1. PRESENTED BY
Mr. SUMAN MANANDHAR
I M.PHARM
DATE: 26TH
AUG 2014
∗ TRANSGENIC ANIMALS & OTHER GENETICALLY PRONE ANIMALS
2. CONTENTS:
● HISTORY
● INTRODUCTION
● PRODUCTION OF TRANSGENIC ANIMALS
● ADVANTAGES
● DISADVANTAGES
● DIFFERENT TRANSGENIC ANIMALS
● CONCERNS AND CONCLUSION
3. HISTORY
The first GMO(Genetically modified organism) was created in 1973 by Stanley N.
Cohen and Herbert Boyer.
The first transgenic animals were mice created by Rudolf Jaenisch in
1974.HE managed to insert foreign DNA into the early-stage mouse embryos.
4. In mid-1974, scientists called for and observed a voluntary
moratorium(delay or suspension of an activity or a law) on
certain recombinant DNA experiments.
One goal of the moratorium was to provide time for a
conference that would evaluate the state of the new
technology and the risks, if any, associated with it. That
conference concluded that recombinant DNA research should
proceed but under strict guidelines.
Cont.…..
5. DEFINITION:
• A transgenic animal is one that carries a foreign
gene that has been deliberately inserted into its
genome.
• Genetic material are altered using techniques in
genetics generally known as recombinant DNA
technology.
6. PRODUCTION OF TRANSGENIC ANIMALS –
THE METHADOLOGY
∗ Step 1 – Construction of a transgene
∗ Transgene is a segment of DNA containing a gene sequence that
has been isolated from one organism and is introduced into a
different organism.
∗ Transgene made of 3 parts:
Promoter: a regulatory sequence that will determine
where and when the transgene is active
Gene to be expressed
Termination sequence: a stop sequence
7. Step 2 – Introduction of foreign gene(transgene) into the
animal
1. DNA microinjection
2. Embryonic stem cell-mediated
gene transfer
3. Retrovirus-mediated gene
transfer
Microinjector
8. ∗ A female animal is super ovulated and eggs are collected.
∗ The eggs are fertilized in vitro.
∗ The transgene containing solution
is injected into the male pronucleus
using a micropipette.
∗ Eggs with the transgenes are kept overnight in an incubator to
develop to a 2 cell stage.
∗ The eggs are then implanted into the uterus of a pseudo - pregnant
female (female which has been mated with a vasectomized male the
previous night)
i. MICROINJECTION METHOD
9. ∗ Transgenic animals can be created by manipulating embryonic
stem cells.
∗ ES cells are obtained from the inner cell mass of a blastocyst.
∗ Transgenic stem cells are grown in vitro.
∗ Then they are inserted into a blastocyst
and implanted into a host’s uterus to grow
normally.
ii. EMBRYONIC STEM CELL METHOD
12. #To increase the probability of expression, gene
transfer is mediated by means of a carrier or vector,
generally a virus.
#Commonly used are Retroviruses because of their
ability to infect host cells.
iii. Retrovirus-mediated gene transfer.
13. contd……
#Offspring derived from this method are chimeric, (single
organism composed of genetically distinct cells.)i.e., not
all cells carry the retrovirus.
#Chimeras are then inbred fo r 1 0 to 20 generatio ns until
ho mo zygo us transgenic animals are obtained and the
transgene is present in every cell.
14. ∗ Step 3: Screening for transgenic positives
∗ Transgenic progenies are screened by PCR(Polymerase chain reaction) to
examine the site of incorporation of the gene
∗ Some transgenes may not be expressed if integrated into a
transcriptionally inactive site.
∗ Step 4: Further animal breeding is done to obtain maximal
expression.
∗ Heterozygous off springs are mated to form homozygous strains.
15. Importance:
Study gene function.
Drug testing.
Research into animal and human disease.
Improve livestock animals.
Use of animals as bioreactors.
Gene pharming, to produce drug in their milk
(e.g.: insulin, cancer drugs) and urine.
Toxicity sensitive transgenic animals to test
chemicals.
Spider silk in milk of goat
16. ADVANTAGES:
Increased growth rate
Increased disease resistance
Increased muscle mass
Increased nutritional quality
Increased food conversion rate
Improved wool quality
Generate large quantities of human proteins in eggs,
milk, blood or urine
Decreased the number of animals used in such
experimentation
17. DISADVANTAGES:
Breeding problem
Multiple functions
Some leads to mutagenicity and functional
disorder
Expensive
Low survival rate
Difficult procedure
18. Rat
Cow
Pig
Sheep
Fish
Goat
Frog
Transgenic animals produced
Brinster's growth hormone mouse
19. Some of transgenic rats:
1. Nude mouse:
•. A nude mouse is a laboratory mouse from a strain with
a genetic mutation that causes a deteriorated or absent
thymus, resulting in an inhibited immune system due to a
greatly reduced number of T cells.
•. The phenotype, or main outward appearance of the mouse
is a lack of body hair, which gives it the "nude" nickname.
•. Valuable to research because it can receive many different
types of tissue and tumor grafts, as it mounts no rejection
response.
20. ∗ It is an animal model of essential (or
primary) hypertension, used to study
cardiovascular disease.
∗ It is the most studied model of
hypertension measured as number of
publications.
∗ The SHR strain was obtained during
the 1960s by Okamoto and
colleagues, who started breeding
Wistar-Kyoto rats with high
blood pressure.
2.Spontaneously hypertensive
rat (SHR)
21. ∗ A “humanized mouse” is a mouse
carrying functioning human genes,
cells, tissues, and/or organs.
∗ Humanized mice are commonly used
as small animal models in biological
and medical research for human
therapeutics.
∗ Humanized mouse models represent
powerful tools for studying
hematopoiesis, inflammatory disease,
viral host-pathogen interactions, and
are helping to accelerate the
development of novel therapies in HIV
infection and oncology.
3. Humanized mouse
22. CONCERNS
Safety - have a potential human health impact in
regards to: allergens, transfer of antibiotic
resistance markers, and other unknown effects
Potential environmental impact - Unintended
transfer of modified genes through cross-
pollination, unknown effects on other organisms in
the environment, and loss of flora and fauna
biodiversity
Ethics- Are we tampering with nature by mixing
genes among species?
Does this create stress for the animal?
23.
24. CONCLUSION:
The creation of transgenic animals has resulted in a shift
from the use of higher-order species such as dogs to lower-
order species such as mice .
It holds great potential in many fields including agriculture,
medicine and industry.
With proper research and careful use the transgenic animals
can go a long way in solving several problems for which
science doesn’t have a solution till now.
