ANALYTICAL AND QUANTITATIVE CYTOPATHOLOGY AND HISTOPATHOLOGY

1. 90
Analytical and Quantitative Cytopathology and Histopathology®
0884-6812/21/4302-0090/$18.00/0 © Science Printers and Publishers, Inc.
Analytical and Quantitative Cytopathology and Histopathology®
OBJECTIVE: To establish a descriptive and comparative
anatomohistological analysis of mice and rats.
STUDY DESIGN: A total of 30 Mus musculus mice
and 15 Rattus norvegicus rats were used. All animals
were kept specific-pathogen-free and absent of surgical
interventions that could cause anatomical and physio-
logical changes.
RESULTS: The study observed species-specific anato-
mohistological characteristics, which will serve as a
basis to assist in choosing the most satisfactory research
model.
CONCLUSION: The evolution of knowledge in bio-
logical and medical areas are attributed to anatomical,
physiological, and immunological studies in animals,
contributing to the discovery of prophylactic measures
and disease treatments that affect humans and ani-
Descriptive Comparative Anatomohistological
Study of the Main Dissected Organs of
Mus musculus and Rattus norvegicus for
Experimental Model Research
Giorgio Silva-Santana, M.M., Licínio Esmeraldo Silva, M.D.,
Jemima Fuentes Ribeiro Silva, M.D., Alexia Gonçalves, M.M.,
Ana Luíza Mattos-Guaraldi, M.D., and Kátia Calvi Lenzi-Almeida, M.D.
From Health Sciences Center, Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil;
Department of Statistics, Institute of Mathematics and Statistics, and Department of Pathology, Medical College, Federal Fluminense
University, Niterói, RJ, Brazil; Department of Histology and Embryology, Biomedical Center, and Laboratory of Diphtheria and Coryne-
bacteria of Clinical Relevance, Faculty of Medical Sciences, University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil; the Collabo-
rating Centre for Reference and Research on Diphtheria/National Health Foundation/Ministry of Health, Brazil; and the Environmental
Science and Conservation Department, Medical College, Federal University of Rio de Janeiro, Macaé, Brazil.
Giorgio Silva-Santana is Doctoral Student, Health Sciences Center, Institute of Microbiology Paulo de Góes, Federal University of Rio de
Janeiro (ORCID ID: 0000-0002-3000-6513).
Licínio Esmeraldo Silva is Professor, Statistics Department, Institute of Mathematics and Statistics, Federal Fluminense University
(ORCID ID: 0000-0003-3861-2806).
Jemima Fuentes Ribeiro Silva is Professor, Histology and Embryology Department, Biomedical Center, University of the State of Rio de
Janeiro (ORCID ID: 0000-0001-7867-3131).
Alexia Gonçalves is Student, Histology and Embryology Department, Biomedical Center, University of the State of Rio de Janeiro.
Ana Luíza Mattos-Guaraldi is Professor, Health Sciences Center, Institute of Microbiology Paulo de Góes, Federal University of Rio de
Janeiro, and Laboratory of Diphtheria and Corynebacteria of Clinical Relevance, Faculty of Medical Sciences, University of the State of
Rio de Janeiro, and the Collaborating Center for Reference and Research on Diphtheria/National Health Foundation/Ministry of Health,
Brazil (ORCID ID: 0000-0003-2522-0416).
Kátia Calvi Lenzi-Almeida is Professor, Environmental Science and Conservation Department, Medical College, Federal University of
Rio de Janeiro, Macaé, and Department of Pathology, Medical College, Federal Fluminense University (ORCID ID: 0000-0003-1097-0927).
This study was financed in part by the National Council for Scientific and Technological Development (CNPq), Coordination for the
Improvement of Higher Level Personnel–Brazil (CAPES) (Finance Code 001), and the Research Support Foundation for the State of Rio
de Janeiro, Brazil (FAPERJ).
Address correspondence to: Giorgio Silva-Santana, M.M., Universidade Federal do Rio de Janeiro, Instituto de Microbiologia Professor
Paulo de Góes, Centro de Ciências da Saúde (CCS), Cidade Universitária–Ilha do Fundão, Rio de Janeiro, Brazil (bio.sant@hotmail.com).
Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.

2. Volume 43, Number 2/April 2021 91
Descriptive Comparative Anatomohistological Study
mals. As mice and rats are the most used animals in
experimental studies, the anatomical and histological
differences between species should be carefully evalu-
ated in order to better apply the study model and avoid
unnecessary waste. (Anal Quant Cytopathol Hist-
pathol 2021;43:90–106)
Keywords: anatomy; experimental model; histo­
logy; mice, laboratory; Mus musculus; rats, labora-
tory; Rattus norvegicus.
Using animals in laboratory research for biological
investigations arose from the study of compara-
tive diseases.1,2 These studies aimed to find sim-
ilarities in the origin and characteristics of the
pathological processes that affected the human
species in animals with the same conditions. Cur-
rently, implementing defined genetically appro-
priate and sanitary laboratory animals has aided
in new discoveries via experimental models, con-
tributing to the prevention of incurable diseases
such as cancers, AIDS, and multiple sclerosis and
also to the development of new surgical treat-
ment techniques. Other applications correspond
to vaccine development, monoclonal antibodies,
evaluation and control of biological products,
pharmacology, toxicology, bacteriology, virology,
and parasitology in addition to basic immunology
studies, immunopathology, organ transplants, and
immunosuppressive drug development.3,4 How-
ever, with technological advances, alternative in
vitro methods, such as cell culture, made it possi-
ble to obtain satisfactory results without relying
on laboratory animals. Nonetheless, animal models
still present advantages, such as providing infor-
mation about the body as a whole.5-8 In regard to
phylogenetic relationship or anatomical conformi-
ty, previous studies have shown that extrapolating
results to humans is not always reliable.7,9-11
Introduced as a laboratory animal in the 19th
century with the Asian species Mus musculus, mice
came to be, from that period on, the most used
animals in experimental studies, becoming an im­
portant experimental model for genetic research.4,12
The Swiss albino lineage is easily accepted and
features heavily in experimental studies due to
its small size, short gestation period, easy domes-
tication and maintenance, and the fact that they
are very prolific.4,13 Eventually, their 99% genet-
ic similarity with humans, allowing to establish
mechanisms involved in human genetic disorders,
and greater capacity of genetic modifications up to
97% of the total of its genes, ensured their labora-
tory use.4
Comprising 137 species from the Central Asia
regions, the genus Rattus have 2 species of great
laboratory importance: Rattus norvegicus (domestic
rat or brown rat) and Rattus rattus (black rat).14 Its
most commonly used species, the albino lineage
Wistar descendant from Rattus norvegicus, devel-
oped at the Wistar Institute in Philadelphia in 1906,
was the first to be implemented as a model organ-
ism at a time when researchers used primarily Mus
musculus mice.15 Heterogenic animals have been
used for various scientific purposes, such as stud-
ies on rheumatology, endocrinology, orthopedics,
and others.16
We consider it of great importance that each
laboratory knows the set of reference values of
its healthy animals according to species, lineage,
genre, and age in order to assist professionals in
their different studies. Thus, the present study
aims to address the general biology of Mus mus-
culus and Rattus norvegicus, establishing a descrip-
tive and comparative analysis of the animals’ main
organs.
Materials and Methods
Ethical Statement and Animals
All experimental procedures described in this
study were approved by the Animal Experimenta-
tion Ethics Committee (CEUA) of the Fluminense
Federal University (UFF) in accordance with Law
no. 11.794/2008 (Arouca law). All procedures used
followed the Brazilian Directive for the Care and
Use of Animals for Scientific and Didactic Pur-
poses of the National Council for Animal Experi-
mentation Control (CONCEA).
This study was conducted per the recommenda-
tions of the National Institutes of Health’s Guide
for the Care and Use of Laboratory Animals. This
study used data obtained from 30 male heterogenic
Mus musculus (Swiss) mice, aged between 60 and
90 days, selected from control groups in a project
approved by the CEUA of the Pro-Rectory of Re­
search, Graduate Programs and Innovation of the
UFF, under protocol no. 439/2013. This study also
used data collected from 15 male heterogenic Rat-
tus norvegicus (Wistar) rats, aged between 90 and
120 days, selected from control groups in a project
approved by the CEUA/UFF under protocol no.
035/2011.
All animals, procured from the Animal Core
Laboratory (NAL), were kept in strict health con-

3. 92 Analytical and Quantitative Cytopathology and Histopathology®
Silva-Santana et al
trol and specific-pathogen-free (SPF). The animals
underwent no surgical intervention that could
cause anatomical changes, nor were they exposed
to any chemical or drug treatment that could alter
their natural physiological state.
Both animals were kept in the NAL/UFF vivar-
ium: the mice in collective cages in groups of 5
and the rats in collective cages in groups of 3.
Both species received commercial ration Nuvilab
CR-1, containing in their composition the nutri-
tional values required, and sterile water (auto-
claved) ad libitum, kept in 12-hour light-dark cy-
cles, with room temperature between 22°C (±2°C)
and 50% humidity, according to laboratory recom-
mendations.
Evaluation of Absolute and Relative Weight
The animals’ absolute weight was measured using
a precision scale (Marte AD2000, maximum load
210 g, sensitivity of 0.01 g).
The animals were euthanized with ketamine
(150 mg/kg) and xylazine (60 mg/kg). After con-
firmation of cardiac and respiratory arrest, absence
of corneal reflex, and drop in body temperature
<25°C,17 they underwent exsanguination by intra-
cardiac puncture for complete removal of blood in
the cardiac chambers, which could interfere with
the hearts’ final weight. Subsequently, a necropsy
was performed for the removal of organs: brain,
heart, lungs, liver, spleen, kidneys, stomach, small
intestine, and large intestine. The eyes were ex-
tracted applying light pressure around the orbital
cavity.
Organ weights were measured using a precision
scale (Sartorius BP 221S, maximum load 220 g,
sensitivity of 0.1 mg), with paired organs (eyes,
lungs, and kidneys) being weighed individually.
Evaluation of Organ Length and Width
The organs were evaluated for their anatomical
form, coloring, length, and width. Each organ was
anatomically positioned to measure length and
width using a titanium pachymeter (Mitutoyo, 6
inches, 150 mm), having as initial point the mid-
line. Subsequently, they were photographed (dig-
ital photographic camera, Sony DSC-W310) and
forwarded for anatomic-histological analysis.
Histology
The organs were sectioned symmetrically in half,
in vertical orientation, positioned in cassettes,
stored in formaldehyde at 10% with pH ~6–7 for
48 hours, and submitted to the dehydration pro-
cesses in growing concentrations of ethanol, diaph-
anization in xylol, and inclusion in paraffin. After-
wards, sections were made with 3 µm thickness
using a microtome (LAB-MR500), using the same
fixed in blade stained with hematoxylin and eosin
(H&E). The slides were observed using optical
microscope (model LX 500) and photographed
using an iVm 5000 camera by the ProgRes pro-
gram capture Pro 2.7.18-20
Statistical Analysis
The variables considered in the study were the
absolute and relative body weights of 2 animal
species and of its organs, besides the length and
width of each organ. The data were statistically
described by mean±standard deviation and es-
tablished the correlation between the weights of
paired organs by Pearson’s correlation coefficient.
Dispersion diagrams were used to allow visual-
izing the weights of the paired organs (lungs and
kidneys) and included the linear regression and
the coefficient of determination R2 of the linear
model. To compare body weights (absolute and
relative) as well as organ weights between spe-
cies, Student’s t test was used (in independent or
paired modality when the data presented normal-
ity), Mann-Whitney U test, or Wilcoxon signed-
rank test (in the absence of normality). Length and
width data comparison of each organ was made
by using the correspondent weights tests. Levene’s
test was carried out to investigate the difference
between numerical data variances of sets. The sta-
tistical analysis was set at 95% confidence interval
(CI) and p=0.05 (5%) level of significance, unless
stated otherwise. PASW version 18.0 acted as sup-
port for the statistical analyses.
Results
Analysis of the Weight, Length, and Width of the
Organs
The statistical description (mean±standard devia­
tion) of the rat and mouse organs’ weight, length,
and width can be observed in Tables I–II. As
expected, given the animal’s physical constitu-
tion, mice presented smaller measures when com-
pared with rats, which was not always verified
when evaluating the relative weights. The anal­
ysis of the relative weight of all organs revealed
statistically significant differences for mice and
rats in the heart, spleen, right and left kidney, right
lung, liver, and large intestine but no statistically

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Descriptive Comparative Anatomohistological Study
significant evidence for left lung, brain, stomach,
and small intestine. Of the significant differences,
the relative weight of the mice’s organs exceeded
that of the rats’ organs, with greater expressive-
ness in the spleen, followed by the heart and other
organs (right and left kidney), with the liver and
large intestine showing smaller expressiveness
(Table I).
When analyzing the correlation of the weights
in paired organs, such as lungs and kidneys, both
species showed strong correlation (all larger than
0.800) (Figure 1). The relation between the Swiss
mice’s lung weight (right and left lung) presented
a coefficient correlation of r=0.960 (p<0.0001) and
r=0.906 (p<0.0001) between the kidney weight
(right and left kidney). For Wistar rats the observed
correlations were r=0.801 (p=0.0003) and r=0.857
(p<0.0001) for lungs and kidneys, respectively.
We found a statistically significant difference
between the Swiss mice’s right and left lung
weight (z=−3.411; value of p=0.001), with mean
difference of 0.057 g and 95% CI for mean differ-
ence of 0.054–0.060. We also observed a statistically
significant difference regarding the weight of the
Table I Absolute and Relative Weight Values
Absolute weight
Comparison of species
Relative weight
Comparison of species
Organ Species
(mean±SD) Statistical test p Value (mean±SD) Statistical test p Value
Body weight Mouse 34.001±1.3031 Student’s t test <0.0001*
(total) Rat 189.39±1.7142 t=346.367;
gl=46
Brain Mouse 0.4415±0.05969 Mann-Whitney <0.0001* 0.0130±0.00143 Mann-Whitney 0.116
Rat 2.7061±0.05916 U=0 0.0143±0.00021 U=142
Eyes Mouse 0.0224±0.00083 Mann-Whitney <0.0001* 0.0007±0.00002 Mann-Whitney 0.0003*
Rat 0.1328±0.00811 U=0 0.0007±0.00004 U=71
Left lung Mouse 0.0801±0.01062 Mann-Whitney <0.0001* 0.0024±0.00026 Mann-Whitney 0.133
Rat 0.4641±0.03702 U=0 0.0024±0.00018 U=279.5
Right lung Mouse 0.1372±0.01833 Student’s t test <0.0001* 0.0040±0.00042 Student’s t test <0.0001*
Rat 0.8127±0.03368 t=–74.362; 0.0043±0.00014 t=–5.566;
gl=17.115 gl=38.725
Heart Mouse 0.1443±0.01734 Mann-Whitney <0.0001* 0.0042±0.00040 Mann-Whitney 0.0001*
Rat 0.7203±0.01118 U=0 0.0038±0.00004 U=81
Liver Mouse 2.0446±0.02832 Mann-Whitney <0.0001* 0.0606±0.00176 Mann-Whitney 0.011**
Rat 11.3733±0.02776 U=0 0.0601±0.00042 U=106
Spleen Mouse 0.1204±0.02476 Student’s t test <0.0001* 0.0035±0.00063 Student’s t test <0.0001*
Rat 0.4366±0.01833 t=–51.978; 0.0023±0.00008 t=10.371;
gl=40 gl=28.257
Left kidney Mouse 0.1982±0.00746 Student’s t test <0.0001* 0.0058±0.00014 Mann-Whitney <0.0001*
Rat
1.0616±0.01314 t=–244.004; 0.0056±0.00005 U=28
gl=16.679
Right Kidney Mouse 0.2542±0.01965 Mann-Whitney <0.0001* 0.0075±0.00047 Mann-Whitney <0.0001*
Rat 1.3479±0.02656 U=0 0.0071±0.00010 U=73.5
Stomach Mouse 0.2823±0.01160 Mann-Whitney <0.0001* 0.0084±0.00022 Mann-Whitney 0.537
Rat 1.5855±0.01120 U=0 0.0084±0.00005 U=178.5
Small intestine Mouse 1.5073±0.01160 Mann-Whitney <0.0001* 0.0402±0.01370 Mann-Whitney 0.077
Rat 8.3373±0.01118 U=0 0.0440±0.00036 U=151
Large intestine Mouse 0.8676±0.01196 Mann-Whitney <0.0001* 0.0257±0.00074 Mann-Whitney 0.007*
Rat 4.8105±0.01153 U=0 0.0254±0.00019 U=101.5
*p<0.01.
**p<0.05.
gl = degree of freedom, SD = standard deviation.

5. 94 Analytical and Quantitative Cytopathology and Histopathology®
Silva-Santana et al
mice’s right and left kidneys (z=−5.025; p<0.0001),
with mean difference of 0.056 g and 95% CI for
mean difference of 0.051–0.061. Regarding Wistar
rats, right and left lungs and kidneys were sta-
tistically different: lungs (p<0.0001), with mean
difference of 0.347 g and 95% CI for mean differ-
ence of 0.336–0.361, and kidneys (p<0.0001), with
mean difference of 0.286 g and 95% CI for mean
difference of 0.277–0.296.
The analysis revealed that, on average, the right
lung of mice is 71.32% heavier than the left lung,
and the right kidney is 28.26% heavier than the
left kidney. Similar data were verified in rats: on
average, the right lung is 75.12% heavier than the
left lung, and the right kidney is 26.97% heavier
than the left kidney.
The comparative analysis between the 2 species’
organ weights revealed significant statistical differ-
ences, with superior values for rats, as expected by
their proportion. The 95% confidence intervals in
Table III reinforce this observation.
Morphoanatomy and Histology
Mice have lissencephalic brains divided into 3 ana-
tomical parts: the hindbrain (rhombencephalon),
which connects the brain to the spinal cord; the
midbrain (mesencephalon), situated between the
other 2 parts; and the forebrain (prosencephalon),
comprising the cerebral cortex (telencephalon),
the diencephalon, and the olfactory bulb. The rat
brain, on the other hand, presents gyrification and
can be divided into the telencephalon (cortex), di-
encephalon, midbrain, bridge, cerebellum, and
bulb. The brain tissue consists of functional cells
(neurons) and support cells (macroglia and microg-
lia) (Figure 2).
In both species the eyes are paired with an almost
spherical shape. The inside out cornea consists of
the outer layer of stratified squamous epithelium
and stroma formed by collagen fibers, fibroblasts,
and some elastic fibers. The vitreous body fills
the space between the lens (almost spherical and
relatively large) and the retina. The lens consists
of laminated fibers formed by modified epithelial
cells, sealed per capsule. Formed by retinal pigment
epithelium, photoreceptor cell layer (containing
mainly rods), outer nuclear layer (containing the
receivers cell nuclei), and outer plexiform layer,
the retina contains intermediate bipolar, horizon­
tal, and amacrine neurons which cross through the
inner layer and the ganglion cell layer forming
the ganglion, where the cells form the axons of
the optic nerve, leading the visual impulses to the
brain. Lastly, the opaque sclera covers the poste-
rior of the eyes (Figure 3).
Their lungs are formed by the bronchi, divided
into bronchioles and alveoli wrapped by capil-
laries, and arteries and veins that follow the bron-
chial tree, with the walls of the pulmonary veins
containing striated heart muscle. While the left
lung consists of 1 lobe, the right lung is sub-
divided into cranial, middle, caudal, and accessory
(Figure 4).
In mammals the heart has 4 chambers: 2 atria
separated by an interatrial septum and 2 ventricles
separated by an interventricular septum. Both spe-
cies’ heart consists almost exclusively of myocytes
inside a fibrous leaf in transversal striated marks
(Figure 5).
The liver comprises 4 main lobes dorsally uni­
ted: a large middle lobe (subdivided by a fissure
in the left and right portions), a right lateral lobe
Table II Length and Width Values
Length (mm) Width (mm)
Organ Species (mean±SD) (mean±SD)
Brain Mouse 13.52±0.54 12.49±0.44
Rat 23.63±0.63 16.73±0.45
Eyes Mouse 3.5±0 (constant radius)
Rat 7.0±0 (constant radius)
Left lung Mouse 11.26±0.56 5.22±0.35
Rat 23.04±1.64 10.67±1.79
Right lung Mouse 13.45±1.19 6.16±0.28
Rat 26.09±1.82 12.04±0.43
Heart Mouse 8.08±0.2 6±0.11
Rat
12.54±0.4
10.01±0.1
Liver Mouse 28.66±0.98 24.46±5.17
Rat 37.37±1.27 42.03±1.03
Spleen Mouse 15.2±0.7 4.64±0.41
Rat 31.89±1.32 6.77±0.39
Left kidney Mouse 10.79±0.83 6.28±0.42
Rat 15.65±2.07 8.57±0.33
Right kidney Mouse 10.74±0.66 6.1±0.43
Rat 16.92±0.97 9.1±0.57
Stomach Mouse 13.02±1.12 5.72±1.01
Rat 25.69±1.32 13.23±1.02
Small intestine Mouse 371.99±1.07 1.87±0.61
Rat 506.06±0.85 5.09±1.03
Large intestine Mouse 116.02±1.12 2.88±0.91
Rat 222.46±1.32 8.09±1.03
SD = standard deviation.

6. Volume 43, Number 2/April 2021 95
Descriptive Comparative Anatomohistological Study
(divided horizontally into anterior and posterior
portions), and a left lateral lobe and caudal lobe.
The latter consists of 2 portions: 1 dorsally, resem-
bling a leaf, and 1 ventrally to the esophagus in
the smallest stomach curve, the surface of which
forms the papillary process. Blood feeds the liver
through interlobular branches of hepatic arteries
and hepatic veins, which are open for the sinu-
soids. The gallbladder sits at the base of the deep
bifurcation of the middle lobe next to the point
of origin of the falciform ligament. Hepatocytes
(parenchymal cells) are placed on plates which
radiate from the central vein to the lobular pe-
riphery (Figure 6).
The spleen is elongated and triangular in cross-
section, with a posterolateral face (diaphragmatic),
a posteromedial face (renal), an anteromedial face
(gastric), and an antero-lower face (colic). Its tis-
sue is formed by parenchyma (splenic pulp), con­
stituted by a differentiated cellular arrangement
into a white pulp (a marginal zone of lower cell
density) and a red pulp (found between the nod-
ules and which constitutes the major part of the
parenchyma) (Figure 7).
Their kidneys are shaped like bean grains with
a dark red coloration. The nephron consists of the
glomerulus surrounded by a Bowman’s capsule,
parietal cells of which appear flattened in the vas­
cular pole and cuboid on the glomerular urinary
pole. Found mainly in the cortex, the proximal
tubules are formed by cuboidal cells with promi-
nent brush-like microvilli. The distal tubules reen-
ter in the cortex and present a cuboid epithelium
similar to that of proximal tubules but deprived of
microvilli (Figure 8).
In rodents the stomach divides into aglandular
and glandular, separated by a pleated margin or
limiting crest (margo plicatus). The glandless por-
tion is of an opaque whitish coloration, coated by
keratinized stratified pavement epithelium. The
glandular portion is translucent, colored reddish-
pink, and coated with simple cubic epithelium.
The mucosa of the glandular stomach encompasses
(1) the cardiac region, located around the gastric
Figure 1 Correlation between weights of the organ pairs. (A) Lungs (right and left) of mice, (B) kidneys (right and left) of mice, (C) lungs
(right and left) of rats, and (D) kidneys (right and left) of rats.

7. 96 Analytical and Quantitative Cytopathology and Histopathology®
Silva-Santana et al
opening of the esophagus extending to the edge
of the pleated margin, containing mucous cells
called cardiac glands, (2) the fundic region (ven-
tral side of the stomach), composed mainly of
glandular mucosa containing fundic glands and
granular eosinophilic parietal cells, which pro-
duce hydrochloric acid, and (3) the pyloric region
extending to the pylorus (sphincter between the
stomach and small intestine), formed by pyloric
mucous glands (Figure 9).
Both species’ intestine is slender and thick, hav-
ing 3 layers in all its length (mucosa with sub-
mucosa, muscular, and serosa). The mucosal epi-
thelium of the small intestine shows scattered
Paneth’s cells, goblet cells, and absorbent cells
forming microvilli, which become smaller and in
greater quantity from the duodenum to the ileum
(Figure 9). The large intestine comprises the ce-
cum, colon, and rectum. The cecum consists of a
corpuscle and an apex, which is more elongated
and less saccular in mice; its mucosa forms trans-
versal folds. The colon has an ascending, a trans­
versal, and a descending part; its mucous mem-
brane contains goblet cells in greater proportion
than in the small intestine, which form crypts with
no villi (Figure 10).
Discussion
Surgical research using laboratory animals has
expanded in recent decades as a result of better
anesthetic support, improved surgery monitoring
infrastructure, and the incessant search for models
capable of reproducing morbid conditions to solve
human diseases.21 Researchers must consider the
Table III Comparison Between Weights of the Organs of Mice and Rats
AHV (Levene’s test) CBOWB-M/R
DBW-A/O
Organ Species MW (g) F statistic p Value AWD (g) SWD (g) t Statistic gl p Value (95% CI)
Brain Mouse 0.442
0.313 0.579 2.265 0.0192 118.169 40 <0.0001** 2.226–2.303
Rat 2.706
Eyes Mouse 0.022
116.055 <0.0001* 0.110 0.0021 52.601 14.165 <0.0001** 0.106–0.115
Rat 0.133
Left lung Mouse 0.077
13.519 0.001* 0.387 0.0097 40.005 14.751 <0.0001** 0.367–0.408
Rat 0.464
Right lung Mouse 0.132
13.546 0.001* 0.681 0.0092 74.362 17.115 <0.0001** 0.662–0.700
Rat 0.813
Heart Mouse 0.139
0.086 0.770 0.582 0.0039 149.742 40 <0.0001** 0.574–0.590
Rat 0.720
Liver Mouse 2.045
0.210 0.649 9.329 0.0091 1029.905 40 <0.0001** 9.310–9.347
Rat 11.373
Spleen Mouse 0.113
0.251 0.619 0.324 0.0062 51.978 40 <0.0001** 0.311–0.336
Rat 0.437
Left kidney Mouse 0.196
6.663 0.014* 0.866 0.0035 244.004 16.679 <0.0001** 0.858–0.873
Rat 1.062
Right kidney Mouse 0.246
14.944 0.0004* 1.102 0.0070 157.667 15.080 <0.0001** 1.087–1.117
Rat 1.348
Stomach Mouse 0.282
0.126 0.725 1.303 0.0037 352.956 40 <0.0001** 1.296–1.311
Rat 1.586
Small intestine Mouse 1.507
0.161 0.691 6.830 0.0037 1850.916 40 <0.0001** 6.823–6.837
Rat 8.337
Large intestine Mouse 0.868
0.155 0.695 3.943 0.0038 1036.818 40 <0.0001** 3.935–3.951
Rat 4.811
*Indicates that variances are unequal (p<0.05).
**Indicates statistical differences highly significant (p<0.01).
AHV = analysis of the homogeneity of variances, AWD = average weight difference, CBOWB-M/R = comparison between organ weights between mice and
rats, DBW-A/O (95% CI) = difference between the weights of animal organs (95% confidence interval), gl = degree of freedom, MW = middle-weight,
SWD = standard weight difference error.

8. Volume 43, Number 2/April 2021 97
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general biology, anatomy, histology, and physiol-
ogy of laboratory animals used in research before
choosing the most appropriate experimental mod­
el. In the course of this article we observed some
Figure 2 Anatomy and histology of the mouse and rat brain. (A–B) Brain of mouse and (E–F) brain of rat (bar=5 mm). Dorsal surfaces
(A and E) and ventral surfaces (B and F) of the cerebral hemispheres. (1) Olfactory bulb, (2) forebrain (prosencephalon), (3) midbrain
(mesencephalon), (4) flocculus, (5) vermis, (6) pyriform cortex, (7) rhombencephalon, (8) longitudinal fissure, (9) cerebral cortex,
(10) caudal colliculus, (11) transverse fissure, (12) optic nerve, (13) olfactory bulb, (14) lateral olfactory tract, (15) optic chiasma,
(16) mamillary bodies, (17) cerebral crus, (18) pons, (19) ventral medial fissure, (20) trapezoid body, (21) paraflocculus, (22) lateral ventral
sulcus, (23) medullary pyramid, (24) medulla oblongata, and (25) spinal medulla. (C–D) Mouse brain tissue, 4× and 40×, respectively
(bar=500 μm). (G–H) Rat brain tissue, 20× and 40×, respectively (bar=500 μm). (1) Cerebral cortex, (2) molecular layer, (3) Purkinje
cells, (4) granular layer, (5) white matter, and (6) sulcus.
Figure 3 Anatomy and histology of the mouse and rat eyes. (A) Eyes (right and left) of mouse and (E) eyes (right and left) of rat (bar=5
mm). (1) Eye globe, (2) optic nerve. (B–D) Tissues that make up eyes of mice, 4×, 10×, and 20×, respectively (bar=500 μm). (F–H) Tissues
that make up eyes of rats, 4×, 10×, and 40×, respectively (bar=500 μm). (1) Cornea, (2) anterior chamber, (3) iris, (4) ciliary body,
(5) lens, (6) vitreous body, (7) retina, (8) sclera, (9) choroid, (10) lamina vitrea, (11) pigmented epithelium, (12) roads and cones, (13) outer
nuclear layer, (14) outer plexiform layer, (15) inner nuclear layer, (16) inner plexiform layer, and (17) ganglion cell.

9. 98 Analytical and Quantitative Cytopathology and Histopathology®
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Mice have lissencephalic brains (devoid of folds),
where the caudate nucleus and the putamen form
important anatomical and histological features
specific to Mus musculus and Rattus norvegicus.
Figure 4 Anatomy and histology of the mouse and rat lungs (right and left). (A–B) Lungs (right and left) of mouse: (A) ventral surface and
(B) dorsal surface. (F–G) Lungs (right and left) of rat: (F) ventral surface and (G) dorsal surface (bar = 5 mm). (1) Left lung, (2) right cranial
lobe, (3) right middle lobe, (4) right caudate lobe, and (5) accessory lobe. (C–E) Pulmonary tissue of mice, 4×, 10×, and 20×, respectively
(bar=500 μm). (H–J) Pulmonary tissue of rat, 4×, 10×, and 20×, respectively (bar=500 μm). (1) Pleura, (2) alveolus, (3) alveolar septum,
(4) bronchioles, (5) pulmonary vein, and (6) bronchial coating epithelial cells.
Figure 5 Anatomy and histology of the mouse and rat heart. (A) Mouse heart and (D) rat heart (bar = 5 mm). (1) Aorta, (2) left auricle,
(3) left ventricle, (4) right auricle, (5) right ventricle, and (6) conoventricular vein. (B–C) Myocardium of the mouse, 10× and 40×,
respectively (bar=500 μm). (E–F) Myocardium of the rat, 10× and 40×, respectively (bar=500 μm). (1) Myocardial fibers exhibit cross
striations formed by alternating segments, (2) myocyte nuclei, and (3) vein.

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Figure 6 Anatomy and histology of the mouse and rat liver. (A) Visceral surface of the mouse liver and (D) visceral surface of the rat liver
(bar=5 mm). (1) Left lateral lobe, (2) caudate lobe, (3) right lateral lobe, (4) right middle lobe, (5) gallbladder, (6) papillary process, and
(7) left middle lobe. (B–C) Hepatic tissue of mice, 10× and 20×, respectively (bar=500 μm). (E–F) Hepatic tissue of rats, 10× and 40×,
respectively (bar=500 μm). (1) Central vein, (2) sinusoid, (3) hepatocyte, (4) portal triad: portal vein, (5) hepatic artery, and (6) bile duct.
Figure 7 Anatomy and histology of the mouse and rat spleen. (A–B) Spleen of a mouse and (E–F) spleen of a rat (bar=5 mm).
(1) Colic surface, (2) gastric surface, (3) diaphragmatic surface, and (4) renal surface. (C–D) Splenic tissue of a mouse, 4× and 20×,
respectively (bar=500 μm), and (G–H) splenic tissue of a rat, 20× and 40×, respectively (bar=500 μm). (1) White pulp, (2) red pulp, and
(3) central artery.

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Figure 8 Anatomy and histology of the mouse and rat kidney. (A) Kidneys (right and left) of a mouse and (D) Kidneys (right and left) of a
rat (bar=5 mm). (1) Papilla, (2) medulla, and (3) cortex. (B–C) Renal cortex of a mouse, 10× and 20×, respectively (bar=500 μm).
(E–F) Renal cortex of a rat, 10× and 40×, respectively (bar=500 μm). (1) Glomerulus, (2) Bowman’s space, (3) renal tubules, (4) capillary,
and (5) mesentery.
Figure 9 Anatomy and histology of the mice and rat stomach and small intestine. (A) Stomach and small intestine of a mouse and
(E) stomach and small intestine of a rat (bar=5 mm). (1) Stomach, (2) duodenum, (3) jejunum, and (4) ileus. (B–D) Stomach of a mouse,
4×, 10×, and 40×, respectively (bar=500 μm). (F–H) Jejunum of a rat, 4×, 10×, and 40×, respectively (bar=500 μm). (1) Mucosa of
the aglandular stomach, (2) main cells, (2a) parietal cells, (3) limiting crest, (4) mucosa of the glandular stomach, (5) villi, (6) absorbent
columnar cells, (7) lamina propria, (8) crypts, (9) submucosa, (9a) muscularis mucosae, (10) muscular layer, (10a) internal circular
muscular layer, (10b) outer longitudinal muscular layer, (11) adventitia, and (12) cardiac gland.

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In mice the rhombencephalon is responsible
for muscle balance and control and autonomous
functions such as heart and respiratory rate.23,24
The midbrain contains structures responsible for
receiving and interpreting visual and auditory
signals.22,24 The hypothalamus controls endocrine
functions and the survival instincts (fight or flight,
reproduction); the thalamus relays sensory infor-
mation to the primary areas of the cortex.23,24 The
fissures and folds that form the cortex, although
abundant in rats and other higher mammals, are
few in mice.23-25 The genes responsible for neural
development in humans and mice are 90% identi-
cal, making the use of these animals in studies of
mental illness of great importance.24
The eyes of both species comprise structures
that nourish, protect, and lubricate the eyeball,
including conjunctiva, eyelids, nictitating mem-
brane (third eyelid), Harderian gland, and Mei-
bomian glands.22-24 Being nocturnal animals, their
retina present peculiarities: a central round area or
“horizontal ray” increases its visual acuity, it also
lacks macula. Under weak light the mouse pupil
a continuous structure (caudate putamen). Com-
monly, the brain of both species can be divided
into 3 anatomical parts: rhombencephalon, mid-
brain, and forebrain. The rhombencephalon, com-
posed of marrow, pons, and cerebellum, connects
the brain to the spinal cord (oblong). The midbrain,
sitting between the hindbrain and the prosenceph-
alon, consists of the tectum, integument, and the
cerebral peduncle. The forebrain encompasses the
cerebral cortex (telencephalon), the basal ganglia,
septum, epithalamus, thalamus, and hypothalamus
(diencephalon) and the olfactory bulb. In the cere-
bral cortex the right and left sides are joined by the
corpus callosum, a thick band of nerve fibers.22,23
The brain tissue consists of functional cells (neu-
rons) and the support cells, macroglia, and microg-
lia. Macroglia are oligodendrocytes (producers of
myelin and astrocytes) present in both gray and
white matter. Ependymal ciliated cells line the
walls of the brain ventricles and can react posi-
tively with astrocytes. The epithelium of the cho-
roid plexus forms microvilli and reacts positively
with epithelial markers.23,24
Figure 10 Anatomy and histology of the mouse and rat large intestine. (A) Large intestine of a mouse and (D) large intestine of a rat
(bar=5 mm). (1) Cecum, (2) colon, and (3) rectum. (B–C) Cecum of a mouse, 10× and 40×, respectively (bar=500 μm). (E–F) Colon of a
rat, 10× and 40×, respectively (bar=500 μm). (1) Serosa (visceral peritoneum), (2) muscular layer, (3) fine submucosa, (4) submucosa,
(5) crypt elongation, (6) Lieberkühn’s glands, (7) goblet cells, and (8) lymphatic follicle.

13. 102 Analytical and Quantitative Cytopathology and Histopathology®
Silva-Santana et al
and left lung weight, directly correlated to the
number of lobes. In mice the right lung can be
71.32% heavier than the left; in rats this differ-
ence can reach 75.12%. Another important ana-
tomical difference is the presence of the accessory
lobe in rats and its absence in mice.
In mammals the heart is divided into 4 cham-
bers: 2 atria separated by an interatrial septum
and 2 ventricles separated by an interventricular
septum.22-24 Between the interatrial septum and
interventricular septum exists a small septal seg-
ment known as the atrioventricular septum (rela­
tively thick and mainly muscular, a result of the
displacement of the atrioventricular valves), placed
between the subaortic segment leaving the left
ventricle.23,24 At the junction between the atria and
ventricles (AVJ) we find 2 valves: the left AVJ has
a mitral valve with 2 separate leaflets (bicuspid
valve), while the right AVJ comprises a valve with
3 separate leaflets (tricuspid valve).22-24 The inter-
nal cover of the ventricles is characterized by
the presence of numerous myocardial protrusions
(trabeculae).23,24 Inside of the apical cavity of the
ventricles, beyond trabeculation and chordae ten­
dineae, we can distinguish fine structures similar
to tendon cords linked to the papillary muscle
(trabeculae tendineae).22-24
The heart consists almost exclusively of myo-
cytes specialized in the conduction system (Pur­
kinje cells) inside a fibrous leaf. The pulmonary
veins join in confluence, entering through a single
foramen on the dorsal wall of the left atrium.23,24
The superior relative weight of the mouse heart
may be correlated with the arrangement of myo-
cardial fibers, with greater quantity of myocardio-
cytes observed in histology. Another important
factor that may explain these results is that the
mouse’s heart rate at rest (~500–780 bpm) is higher
than the rat’s (~250–480 bpm).4,36,37
The liver occupies one-third of the anterior re-
gion of the abdominal cavity, presenting a surface
covered by a capsule, formed by conjunctive tis-
sue.23-25 The blood flows from the perilobular re-
gion to the central vein, following to the cava vein
via large hepatic veins. The hepatocytes are dis­
tributed on plates radiating from the central vein
to the lobular periphery; the sinusoidal coating
cells (endothelial cells, Kupffer cells, fixed macro-
phages linked to sinusoid wall cells, and granular
lymphocytes with natural killer activity) show ac-
cumulation of cytoplasmic lipid and vitamin A, he-
matopoietic cells, bile duct cells, connective tissue
widens to 1.2 mm in diameter, while in strong
light it contracts about 0.2 mm diameter for half
a second.24,26,27 It can have 2 types of photorecep-
tors: rods, which detect light and darkness, and
cones for green and blue colors. As blue cones
are sensitive to short wavelengths, both animals
can see ultraviolet.4,28 Each neural cell on the
rodent’s retina has a greater number of photore­
ceptors than that in humans, i.e., the ganglionic
receptor fields of the rodent’s cells are greater
than those of the human fovea,29 which increases
sensitivity and reduces acuity. Present only in
albino mice, the Bowman’s membrane has both
pigmentation and retinal pigment epithelium.23,24
The mouse sclera is opaque, covering from the
back of the eyes to the choroids, with no tapetum
lucidum.23-25 The ciliary body, iris, and choroid
form the external fibrous vascular tunic (uvea)
containing pigment, except in albino species.23-25
The lens consists of rolled fibers formed by modi-
fied epithelial cells, enclosed per capsule, allowing
for almost all visible light and 50% of ultravio-
let.23,30 Its poorly developed ciliary muscle renders
it impossible to change the shape of the lens26,31
unless administered atropine drops, which relax
the lens keeping its focus, but these are inconclu-
sive data.31,32 Lastly, the nictitating membrane
forms a translucent conjunctiva that, together with
the Harderian gland, surrounds and protects the
optic nerve.23,24
Located in the thoracic cavity, covered by the
parietal pleura, the left lung consists of a single
lobe, while the right lung consists of 4 lobes (cra-
nial, middle, caudal, and accessory), with stud-
ies describing at least 9 standards for pulmonary
lobulation.23,24,33,34 Two bronchi form an intrapul-
monary route with bifurcations ending in bron­
chioles. The smallest bronchial airways in mice
are the terminal bronchioles, which evolve into al-
veolar ducts (alveolar sacs and alveoli). The alve-
olar epithelium consists of lung cells type I and cu-
boidal cell type II. Lungs of healthy mice present
few lymphoid tissues (bronchus-associated lym-
phoid tissue [BALT] associated with bronchial tis-
sue), becoming well developed only by pathogen-
ic infections.23,24,35 Blood enters the lungs from the
systemic circulation through the bronchial arter-
ies, and venous blood exits through the pulmo-
nary arteries of the heart. Arteries and veins end
on the bronchial tree, and the walls of the pulmo-
nary veins contain cardiac muscles (striated).23,24
We found a significant difference between right

14. Volume 43, Number 2/April 2021 103
Descriptive Comparative Anatomohistological Study
and macrophages that, when stimulated by an
antigen, can store plasma cells. In continuations
of the periarteriolar lymphoid sheath, found in bi-
furcations of the central arterioles, the follicles
comprise mainly B lymphocytes, follicular den-
dritic cells, and T CD4+ cells in smaller number;
commonly, T CD8+ cells are absent.39,43 When
stimulated by antigens, follicles can form germinal
centers with a greater presence of follicular macro-
phages.39,40 Lastly, situated in the interface of red
pulp with the periarteriolar lymphoid sheath and
the follicles, the marginal zone consists of reticular
fibrils, macrophages, dendritic cells, and medium
B cells.41,44 The macrophages of the marginal zone
assist in removing microorganisms and virus, rec-
ognizing receptors (TLRs) and recognizing bac-
teria.39,44 The marginal zone B cells are a unique
subset of noncirculating B cells that have an IgM+/
IgD− phenotype as opposed to follicular B cells,
which are IgM+/IgD+.39,43
Kidneys lie parallel in the dorsal part of the
abdominal cavity; the right kidney is slightly high-
er (cranially) than the left kidney.22-24 The right
kidney is usually larger than the left, and the kid-
neys of males are relatively larger than those of
females.24 This article corroborates these findings,
as the right kidney of mice showed, on average,
28.26% more weight than the left, with similar
results observed in the right kidney of rats, on
average 26.97% heavier than the left.
In rats, the kidney is unilobed with a single
papilla, formed by the cortex and medulla. The
cortex contains cortical tubular labyrinths (mainly
proximal convoluted tubules) and medullary rays
that extend from the external medulla.23 The me-
dulla is subdivided into an outer zone, with one
external and internal band and an internal zone
forming the papilla. Its functional unit is the neph-
ron, which consists of the glomerulus (covered by
Bowman’s capsule) wound around the proximal
and distal tubules, the descending and ascending
portions of the Henle loop and the straight por-
tions.24 The nephrons connect into the collecting
ducts, which emerge from the papillary ducts,22,23
which in turn open at the tip of the renal papilla
in the renal pelvis.24 The renal pelvis is lined with
transitional cell epithelium, and its continuation
forms the ureter.22 The renal papilla in rats can
be long and protrudes into the initial portion of
the ureter.23 Most rat species may exhibit sexual
dimorphism under the influence of testosterone
(the female parietal epithelial cells are typically
cells, and blood vessel wall cells (adventitial cells
and smooth muscle).23,24 A characteristic usually
found in hepatic cells of rats and mice is anisocy-
tosis and anisokaryosis (variations in the size of
cells and nuclei).24
Observed only in mice, the gallbladder sits at
the base of the deep bifurcation of the middle lobe
next to the point of origin of the falciform liga-
ment.23,24,38 Both the hepatic duct of the liver and
the cystic duct of the gallbladder join to form the
common bile duct—the standard hepatic pattern,
although studies have described at least 13 dif-
ferent ones.33 In rats the periportal biliary system
consists of a network of canaliculi that end in a
common bile duct.21
Of friable consistency and purple coloration,
the spleen rests on the left dorsocranial region of
the abdominal cavity, posterior to the stomach
and above the upper pole of the left kidney.22,23,39
Both the greater intensity of the color purple found
in the spleens of rats and the superior relative
weight of the mouse spleen can be attributed to
the venous sinuses (hematopoietic tissue)—they
are bigger and more abundant in rats, generating
numerous anastomoses (sinus) that provide larger
areas of red pulp, unlike the venous sinuses in
mice.39 Mice showed a greater proportion of
white pulp than did rats.39,40 Finally, extramedul-
lary hematopoiesis is common in the red pulp of
rodents, with greater prevalence in the spleens of
mice than that in rats.39
This organ acts as an immunological system
and blood reservoir, producing and maturing B
and T lymphocytes, integrating, in some cases,
the reticuloendothelial system and participating
in the hematopoiesis and eryptosis process (reno-
vation of red blood cells).39 The red pulp consists
of reticular tissue formed of splenic cords (or
Cords of Billroth) and venous sinuses (splenic
sinuses), which go to the blood tissue (capillaries
and sinusoids); the leukocytes perform its selec-
tions and destruction, if they present anomalies,
are old or injured. Besides serving as a leukocyte
and platelet deposit, the macrophages contained
therein are responsible for the phagocytosis of
microorganisms.24,39,41 The white flesh comprises
a periarteriolar lymphoid sheath, follicles, and
marginal zone.41,42 The internal periarteriolar lym-
phoid sheath consists predominantly of T CD4+
cells, T CD8+ cells in smaller number, dendritic
cells, and migrating B cells; its outer part consists
of small/medium lymphocytes (B and T cells)

15. 104 Analytical and Quantitative Cytopathology and Histopathology®
Silva-Santana et al
thelium lining and a fibrovascular stroma called
“own blade,” separated from the submucosa by
mucosal muscular lamina (a thin layer of smooth
muscle).23,24 The submucosa consists of connec-
tive tissue involving blood vessels, lymphatic ves-
sels, and nerves. The muscular layer consists of
the muscle inner circular layer, and the serosa com-
prise the thin layer of the peritoneum.23,24,38
Its lymphoid tissue (gut-associated lymphoid tis-
sue) forms the scattered nodules, the submucosa,
and the lamina propria. Located over the mesen­
teric accessory of the small intestine are the aggre-
gated lymphoid nodules (Peyer’s patches); on the
surface of the epithelium of the antimesenteric
portion we find antigen-producing M cells.45 In the
large intestine the Peyer’s patches can be antimes-
enteric or not. The mucosal epithelium usually
has absorption cells, with luminal membrane cells
forming microvilli, and a greater number of goblet
cells than in the small intestine, forming crypts.
Rats show a greater number of Paneth cells, which
contain eosinophils (granulocytes) with lysozyme
and antimicrobial peptides. Polypeptide entero-
endocrine cells appear scattered along the gastro-
intestinal tract, and caveolae cells are responsible
for producing intestinal chemoreceptors.23,24 The
entrance of the ileum forms the sacculus rotundus
and the exit of the colon forms the ampulla coli.24
Different from higher mammals, the mucosal
surface of the small intestine of rats has no folds
(plicae). Instead, the mucosa forms villi from epi-
thelium and lamina propria, forming the inner
intestinal lumen23,24,38; the villi, each containing 1
lymphatic vessel, decreases in number from the
duodenum to the ileum.23,24 Between the villi, pro-
trusions emerge in the opposite direction under
the surface of the mucosa, forming crypts or intes-
tinal glands.23,24,38
Both species have a functional cecum, large in
size, with sacs forming a fermentation tank where
specialized microorganisms degrade cell walls
formed by cellulose. In rats the cecum has a cor-
puscle and an apex; its mucosa forms transversal
folds.45 The colon has an ascending, a transversal,
and a descending part and a mucosa consisting of
an ascending and transversal part, which forms
transversal folds. The descending colon and rectum
consist of longitudinal protuberances prominent in
the lumen, formed by the mucosa and submucosa.
The muscular mucosa is more prominent in the
rectum than in the colon. From rectum to anus,
the superficial epithelium becomes squamous and
flattened and the male parietal epithelium can be
both cuboidal and flattened).22,24
Regardless of the genus, the parietal cells of
Bowman’s capsule are flattened in the vascular
pole and cuboidal in the urinary pole of the glom-
eruli.23,24 The proximal tubules, found mainly in the
cortex, consist of cuboidal cells with a prominent
brush-like border (microvilli).22,23 The descend-
ing and ascending portions of the Henle loop are
found in the marrow, lined with flattened epithe­
lium that resembles the endothelium of blood
vessels.24 The distal tubules reenter the cortex and
consist of a cuboidal epithelium similar to that
of proximal tubules but devoid of microvilli.22
The straight portion of the distal tubules leads to
dense macula in the vascular pole of the glomer-
ulus, where specialized cells produce renin.24 In
rats, the renal vasculature resembles other spe-
cies: the branches of the renal artery fashion the
arcuate arteries on the corticomedullary border.23
The interlobular branches of the arched arteries
supply the afferent arterioles of the glomeruli,22,24
which in turn provide the cortex with blood and
form the downward straight vessel, responsible for
supplying blood to the marrow.23,24 The ascending
vessel collects venous blood, while spontaneous
vacuolation occurs in the arched interlobular veins,
probably of lysosomal origin, in the renal tubular
epithelium of the external medulla.22,23
In rodents, the stomach divides into glandular
and nonglandular.24,38,45 The nonglandular stom-
ach usually has thin, transparent walls lined with
keratinized, stratified squamous epithelium, serv-
ing for storage and food digestion. The glandular
stomach has thick walls lined with epithelium;
the blade itself consists of tubular gastric glands
containing cells that secrete mucus and pepsino-
gen, main cells, and hydrochloric acid–producing
cells (parietal cells).21,23,24,45 The initial portion of
the duodenum has special tubular alveolar glands
known as Brunner glands.23,24 One or more pan-
creatic ducts and the common bile duct end in
the duodenal papilla.24 Models used to replicate
stomach ulcers should consider inducing ulcers in
the nonsecretory mucosa; such studies must un­
dergo rigorous evaluation, as producing ulcers
in the rat’s gastric mucosa is a difficult task, and
most proposed methods frequently end in animal
suffering.21
The intestine is slender and thick, having 3 lay-
ers in all its length (mucosa with submucosa, mus-
cular, and serosa).23,24,38 The mucosa has an epi­

16. Volume 43, Number 2/April 2021 105
Descriptive Comparative Anatomohistological Study
Criação e experimentação. Rio de Janeiro, Fiocruz, 2006, p
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17. Lima JBA, Skare TL, Malafaia O, Ribas-Filho JM, Michaelis
T, Ribas FM, Macedo RAC: Sepsis inducing syndrome of
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18. Silva-Santana G, Lenzi-Almeida KC, Fernandes-Santos C,
Couto DS, Paes-De-Almeida EC, Aguiar-Alves F: Mice
infection by methicillin-resistant Staphylococcus aureus from
different colonization sites in humans resulting in diffusion
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19. Silva-Santana G, Lenzi-Almeida KC, Lopes VGS, Aguiar-
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stratified, presenting sebaceous modified glands
(circum-anal gland) around the anus.23,24,38
Conclusion
Except for some veterinary and zoology books,
few are the studies focusing on the specific char-
acteristics between laboratory animals. Today we
can dispose of more refined experimental models,
maintaining and intensifying specific phenotypic
and genotypic characteristics, since the animal’s
genome results from directed mating. The greater
the similarity between the animal’s physiologi-
cal, anatomical, and organic characteristics with
humans, the greater its applicability in studies
and the reliability of results, even if establishing
reliable general rules to validate the extrapolation
from one species to another is infeasible.
Mice and rats are the species most used in
research. They are better known scientifically and
present advantages over other species, such as
smaller physical size and greater weight, easy
mobility, and lower maintenance cost. Currently,
multiple lineages of mice and rats destined to dif-
ferent research purposes exist. However, studies
using animals require careful research planning,
knowledge of the country’s laws and guidelines,
ethical principles, and, above all, being up-to-date
on previous studies in the same area so as to avoid
repetitive tests and inconclusive results, which
would lead to waste, thus allowing to choose the
most suitable species.
With technological advances, alternative re-
search methods, such as in vitro, are being devel-
oped, but experimental models using laboratory
animals still pose the advantage of obtaining in-
formation about the organism as a whole.
Acknowledgements
We would like to thank the Pathology Program at
Fluminense Federal University (UFF), the Institute
of Microbiology Paulo de Góes at Federal Univer-
sity of Rio de Janeiro, and the Laboratory of Diph-
theria and Corynebacteria of Clinical Relevance at
the University of the State of Rio de Janeiro (UERJ).
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