https://insidescientific.com/webinar/improving-animal-modeling-24/7-home-cage-monitoring-bioexclusion-biocontainment-mouse-housing-system-tecniplast
Recently, a surging response to the COVID-19 pandemic has led to an exponential increase in study support for biocontainment and bioexclusion research. Mouse models are being rapidly developed in both areas, and biosafe housing of these animal models is critical. Additionally, non-invasive home cage monitoring can improve the translational value of these research models.
Locomotor activity patterns can be monitored 24/7 as a diagnostic tool for biosecurity studies. Researchers, staff and animals alike will also benefit from a decreased need for animal handling, caging manipulations and animal monitoring.
This webinar will be most valuable for institutions where biocontainment and bioexclusion work is being considered or conducted, and for researchers who wish to better understand what can be achieved through continuous measurement of animal welfare based of use of non-invasive activity monitoring.
Improving Animal Modeling with 24/7 Home Cage Monitoring in Bioexclusion & Biocontainment Mouse Housing Systems
1. John Hasenau, DVM, DACLAM
Labanimalconsultants@charter.net
CEO and Principal Consultant,
Lab Animal Consultants
Stefano Gaburro, PhD
stefano.gaburro@tecniplast.it
Scientific Director, Digilab Division,
Tecniplast S.p.A.
Improving Animal Modeling with
24/7 Home Cage Monitoring in
Bioexclusion & Biocontainment
Mouse Housing Systems
2. Improving Animal Modeling with
24/7 Home Cage Monitoring in
Bioexclusion & Biocontainment
Mouse Housing Systems
Experts discuss current biosafety
requirements and what home cage
monitoring can teach us in bioexclusion
and biocontainment studies.
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5. Bioexclusion and Biocontainment, are they
mutually exclusive with current rodent
housing systems?
Copyright 2020 J.Hasenau, Tecniplast and InsideScientific. All Rights Reserved.
John Hasenau, DVM DACLAM
CEO and Principal Consultant,
Lab Animal Consultants
E-mail: labanimalconsultants@charter.net
6. • How to accelerate bioexclusion and biocontainment research outcomes through
advanced caging systems.
• What are the practical differences in bioexclusion and biocontainment caging systems.
• Learn how locomotor activity serves as a “digital biomarker” for animal welfare for
infectious disease and metabolism studies.
• Understand how to improve the translational value of animal models via home
cage monitoring.
• Practical relevant information that you (the participants) can use at your facilities.
Key Objectives
8. The Human Microbiome Project
An initiative of the NIH Roadmap for Biomedical Research
1st Phase of HMP (FY2007-2012) focused on the development of
metagenomics datasets and computational tools for
characterizing the microbiome in healthy adults and in cohorts of
specific microbiome-associated diseases
https://www.hmpdacc.org/
2007–2015: Exploration
The Human Microbiome Project
9. The Great Wave
Katsushika Hokusai (1760 –1849)
“Ology”
Gnotobiotics Microbiomics
With permission from Betty Theriault “Where is a mouse to live” FELASA 2019
What Changed in Research Paradigms?
“Omics”
10. September 3, 2018:
Pubmed Search “Microbiome” = 45,497 “hits” beginning in 1956
“Gnotobiotics” = 15,575 “hits” beginning in 1946
Narrow Range to 2005 – 2018 = 44,375 “Microbiome”
4,824 “Gnotobiotics”
Focus on Gnotobiotics - Bioexclusions
12. Mechanistic understanding of host-microbiome interactions
Wladarska et al, Cell 2014
Suez et al, Nature 2014
Thaiss et al, Cell 2014
Korem et al, Science 2015
Levy et al, Cell 2015
Zeevi et al, Cell 2015
Thaiss et al, Nature 2016
Gury et al, Cell 2016
Thaiss et al, Cell 2016
Korem et al, Cell Metab. 2017
Rothschild et al, Nature 2018
Thaiss et al, Science 2018
Suez et al, Cell 2018
Zmora et al, Cell 2018
Principles of microbiome-mediated disease treatment
13. Kennedy, Allergy Rhinol. 2020
Bassiouni et al, Infect Microbiol. 2020
Carney et al, Methods in Lung Microbiome
Research 2019
Hufnagl et al, Seminars in
Immunopathology 2020
Aguilera et al, Front. Immunol.
2020
Voskamp et al, Seminars in
Immunopathology , 2020
Bassiouni et al, Front. Cell. Infect.
Microbiol. 2020
Tan, Front. Cell Dev. Biol. 2020
Mechanistic understanding of host-microbiome interactions
Principles of microbiome-mediated disease treatment
14. Flexible Film Isolator
Present
Pre-1960
~1960
Germ Free Housing
Top photo depicts LOBUND Stainless Steel Isolators
Examples of early models of flexible film isolators
introduced by Philip Trexler at the LOBUND Institute.
The Laboratory Rat, Vol. 2 2006.
Hermetically sealed systems
15. Breeding and maintenance for long term housing of GF requires sterile conditions, which are easiest fulfill in
positive pressure isolators.
A GF breeding facility
16. Large isolators for breeding Wild Type mice Small isolators for maintaining Genetically
Manipulated GF mice strains
More Examples of GF breeding facilities
24. Gnoto Facility – Validated Experimental Procedures
Different types of
procedures can be
performed in the
ISOcage P or N
System.
Type of procedure
Cages
Specific diet provision
Specific water provision
Animals
Routine change
Feces collection
Body weight measurement
Body temperature measurement
Buccal swab
Intra-peritoneal injection
Gavage
Blood collection
Time-pregnancy mating
Surgery (vasectomy)
Surgery (renal ischemia-reperfusion)
Fetus transfer/ Axenization
Courtesy of Joana Bom,
Axenic/Gnotobiology Facility Manager
26. Gnoto Facility – Experimental Diversity
Axenic Mice
. Sentinels
. Breedings
. New axenizations
. Experimental
Mono/bi colonized
Mice
. Experimental
Total fecal transplant
or Controlled
microbiota SOPF Mice
. ExperimentalCourtesy of Joana Bom,
Axenic/Gnotobiology Facility Manager
27. 4. ISOcage placed in the Gnotorack
until manipulation.
5. For animal manipulation on the IBS,
ISOcage undergoes a disinfection cycle.
1. ISOcage autoclaved
inside a cylinder.
3. ISOcage with axenic animals to
be transferred to the Gnotorack.2. Cylinder connected to the isolator to
remove animals.
7. Animals ready for manipulation,
or to be moved to Isolator trough an
autoclaved cylinder.
6. Inside the IBS, the cage is
removed from the dunk tank.
The Bioexclusion/Bioinclusion WorkflowAxenicGnoto
Courtesy of Joana Bom,
Axenic/Gnotobiology
Facility Manager
31. Keep the animals in their home cage: reduce animal and cage handling
Automated 24/7 data collection from the home cage-home provides unique advantages
DVC® for ISO
ResearchFacility Management /
Animal Welfare
24/7 locomotor detection for a
better daily animal welfare
check
Reduce the Bedding change
cage handling
Automatic flooding detection
24/7 locomotor data collection for more
reliable data
High throughput data (all the experiment
cages together) minimize possible
confounding factors
Provide standardized metrics: just keep the
animals in the home cage and automatically
collect results (reduced bias).
33. What can Home Cage Monitoring
Teach us in Biosafety Studies ?
Copyright 2020 S. Gaburro, Tecniplast and InsideScientific. All Rights Reserved.
Scientific Director, Digilab Division,
Tecniplast S.p.A.
Stefano Gaburro, PhD
E-mail: stefano.gaburro@tecniplast.it
Linkedin: https://www.linkedin.com/in/stefanogaburro
34. Mice spend 99% of their
time in the home cage.
More active at night
Most experiments
during daytime
Enviromental factors
(cage change, personnel)
are often
underconsidered
Cage change effects,
Weaning
effects longitudinal
studies (genetics*age)
Locomotion/Activity
behavioral test are
outside home cage
Only Snapshot,
Animal Welfare?
The experimental use of animals is evolving
35. Automated 24/7 data collection from the
home cage-home provides several advantages:
Keep animals in their home cage:
reduce animal handling
Allow animals monitoring during periods
generally not observed (e.g. nighttime)
High throughput data: several available IVC
Cages running in parallel.
Provide standardized metrics: just keep the
animals in the home cage and automatically
collect results (reduced bias).
Tecniplast Vision: Automated Home Cage Monitoring
39. Empower your current ISOcage Units with the DVC® technology !!!
DVC® in Biocontainment Settings
40. Automated 24/7 data collection from the home cage-home provides unique advantages
DVC® for ISO
ResearchFacility Management /
Animal Welfare
Keep the animals in their home cage: reduce animal and cage handling
24/7 locomotor detection for a
better daily animal welfare
check
Reduce the Bedding change
cage handling
Automatic flooding detection
24/7 locomotor data collection for more
reliable data
High throughput data (all the experiment
cages together) minimize possible
confounding factors
Provide standardized metrics: just keep the
animals in the home cage and automatically
collect results (reduced bias).
43. 1. NHP and Larger
animals are
expensive
2. Ethical concern in
large animals or
NO SCALABILITY
Infectious disease animal models: Covid19 model...other considerations
44. Revisited Covid19 mouse model
Embryos cryopreserved @ Jax
Available Soon!
Why is ACE2 receptor important
for Covid19 entrance?
Animals kept 5 years,
then culled!
48. IVC*
What can we do with those models?
Isolators
Keep animals and visual inspection?
Measure sponteneous
locomotion in mice...
Why is it so important?
*Only permitted upon certain urgent conditions and by certain Nations
DVC®
ISO/N
50. International Multicentric study including Jackson Lab (D)
C57BL6J – 4 animals/cage (female)
24/7 Locomotor Activity
Night
Day
Locomotoractivity
Age (Days)
Clear diurnal (day-night) locomotor activity differences!
What does a normal locomotor activity profile look like?
51. Virus (H1N1, Coronavirus, Spanish Flu), activity
and temperature acquired through minimiter
(implanted device)
Hypothermia (possibly lethargy) and loss of circadian locomotor activity
BODY TEMPERATURE LOCOMOTOR ACTIVITY
Viral effects of coronavirus on body temperature and activity
52. Control Vaccine Virus
LOCOMOTOR ACTIVITY
Balb/c mice (Venezuelan equine encephalitis virus)
Activity and Temperature through
Same activity
pattern of
vaccine treated
animal as for
control vs.
infected!!
Control Vaccine Virus
BODY TEMPERATURE
Vaccine effects monitored in the home cage
53. Locomotor activity seems to demonstrate to
be predictive of virus pathological-induced effects
and its reversal by efficious vaccine
DVC® has been used in the past by Jackson Labs to assess
locomotor activity in normal C57BL6/J mice
Since the technology applied to biocontaiment is new, we lack
of data but we collected data from other pathological animals
models.
DVC® and locomotor activity in infectious disease
54. SCID mice (n=216)
Groups (cages) of 3-4-5 mice treated with cytostatic drug (cancer therapy) (200 mg/kg IP, 10mL/kg)
Body Weight
Hypoactivity
(-50%)
is detected prior
the onset of
body weight loss
(-3,5%)
Activity
Hypoactivity anticipates body weight reduction
55. Locomotor activity demonstrates a great potential to additional
diagnostic tool in infectious disease as well to other experimental settings.
DVC® might reduce needless cage opening and therefore minimizing viral
exposure.
Core body temperature (implanted or rectal thermometer) or body
weight, at least in rodents, should be used in adjunction to locomotor
activity to assess reliably animal welfare in such study type.
Biocontainment Conclusions
56. Cryan et. Al, Lancet Neurology
Metabolism studies have gained major interest regarding dietary
effects on psychiatric disorders.
Many of such studies are performed in immunocompromised mice
(e.g. fecal microbial transplantation in left picture to study effects on
psychiatric disorders).
Surgery is performed in such animals and correctly assessing the
recovery represents an important aspect of animal welfare.
DVC® in Metabolism Research: Gnotobiotics
57. Total activity periphery duration is confirmatory of DVC® findings!!
Open FieldDVC® (day)
Confirmatory findings in Germ free animals: ADHD animal model
59. DVC® can help to detect sick animals in infectious disease studies (e.g. COVID-19 article)
DVC® can aid to detect and confirm locomotor activity patterns in germ-free or nude mice used
for gnotobiotics’ research
Technology already validated (as for vaccine going to humans, e.g. Moderna- no animal
validation needed).
DVC® system for ISOcage units P and N represents a unique opportunity to empower these equipment and provide
useful 24/7 data for scientists in biocontainment and bioexclusion research fields.
Final Conclusions
For more information on Tecniplast solutions, please visit www.tecniplast.it or write to digilab-mktg@tecniplast.it
60. John Hasenau, DVM DACLAM
Labanimalconsultants@charter.net
CEO and Principal Consultant,
Lab Animal Consultants
Stefano Gaburro, PhD
stefano.gaburro@tecniplast.it
Scientific Director, Digilab Division,
Tecniplast S.p.A.
Thank You!
To learn more about digital housing solutiosn from
Tecniplast, please visit:
https://www.tecniplast.it/en/catalog/digilab.html
Editor's Notes
Please double-check the copyright text in this slide.
For 5 years different types of procedures in this system, from basic manipulation (bottom change; water and food supply) to specific procedures (gavage and regular feces collection) and sophisticated surgeries. These procedures are validated because the animals maintain their status.
So, the axenic animals are produced in Isolators and then are transferred to the ISOcageP IVC racks to undergo Gnotobiology experiments. We stablished a workflow: animals are moved from isolators to ISOcages upon user request, or whenever space is needed inside the Isolators for new weanings or breedings.