JAX Mice and Services

Upcoming JAX Webinars™
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January 23, 2014, 1pm ET
Keep Track of Your Mice: The JAX Colony Management
System (JCMS) Database Live Tutorial
January 30, 2014, 1pm ET
Breakthrough Models for Type 1 Diabetes Research: from
NOD to Humanized Mice
www.jax.org/jaxmice/webinar |
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Make your life in the lab easier
MouseClique Blog
mouseclique.jax.org |
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Everything but the
Experiment:
Tips for Working
with Diabetic Mice
Technical Information Services
The Jackson Laboratory’s Mission
Performing Research
Investigating genetics and biology of human disease
Providing Resources
JAX® Mice Clinical & Research Services, bioinformatics data,
technical publications and more…
Educating Scientists
World-class courses, internships and other programs
www.jax.org/courses |
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® Mice
JAX
JAX® Mice
TheGold
Gold Standard
Standard for
The
forBiomedical
BiomedicalResearch
Research
NIH funded resource
>7,000 strains and growing
Unsurpassed genetic quality & animal health
Best characterized & referenced ~100 new pubs/week
Common inbred strains (C57BL/6J, BALB/cJ, DBA/2J) support
development/collection of specialty strains and other valuable
community research resources
JAX® Mice |
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Online Resources to Expedite
Research
JAX® Mice Database
www.jax.org/jaxmice/query
www.jax.org/jaxmice/support/techsupport-index |
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Online Resources to Expedite
Research
JAX® Mice Database
www.jax.org/jaxmice/query
Mouse Genome Informatics
www.informatics.jax.org
www.jax.org/jaxmice/support/techsupport-index |
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Online Resources to Expedite
Research
JAX® Mice Database
www.jax.org/jaxmice/query
Mouse Genome Informatics
www.informatics.jax.org
Mouse Phenome Database
www.jax.org/phenome
And many more unique
resources
www.jax.org/jaxmice/support/techsupport-index |
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Tips for Working with Diabetic Mice
Smart experimental design
Actively minimize distress
o
o
o
o
What is distress?
Why should we care?
Experimental manipulations
Routine husbandry
JAX® Mice |
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Tips for Working with Diabetic Mice
Smart experimental design
Actively minimize distress
o
o
o
o
What is distress?
Why should we care?
Experimental manipulations
Routine husbandry
JAX® Mice |
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Common Experimental Design
Blunders
Inadequate sample size
Inexact data collection
Casual selection of control mice
JAX® Mice |
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Mouse Sample Size Considerations
Overall disease incidence rate
Length of study
Synchronous or asynchronous disease onset
JAX® Mice |
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Mouse Sample Size Considerations
Overall disease incidence rate
Length of study
Synchronous or asynchronous disease onset
 Do a power analysis
 Include extra mice
JAX® Mice |
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Blood Analysis Considerations
Blood values
vary throughout
the day
C57BL/6 Blood Glucose Analysis
Collection
method effects
results
Blood glucose is lower when collected from
retro-orbital relative to tail vein
Rogers IT et al. 1999. Contemp Top Lab Anim Sci 38(6):25-28. PMID:12086443
JAX® Mice |
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Blood Analysis Considerations
Blood values
vary throughout
the day
C57BL/6 Blood Glucose Analysis
Collection
method effects
results
 Sample at the same time of day
 Sample from the same route
Rogers IT et al. 1999. Contemp Top Lab Anim Sci 38(6):25-28. PMID:12086443
JAX® Mice |
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Selecting a Control Strain
Littermate mice
Inbred strain
Related inbred strain
F2 Hybrid
NOD/ShiLtJ (001976)
Control Strains for NOD/LtJ Mice in Diabetes Research
jaxmice.jax.org/jaxnotes/archive/477a
JAX® Mice |
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Selecting a Control Strain
Littermate mice
Inbred strain
Related inbred strain
F2 Hybrid
NOD/ShiLtJ (001976)
 Consult the literature for the most appropriate
and acceptable control strain
Control Strains for NOD/LtJ Mice in Diabetes Research
jaxmice.jax.org/jaxnotes/archive/477a
JAX® Mice |
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Checklist to Avoid Experimental
Blunders
 Do a power analysis to determine sample size
 Include extra mice to account for outliers/nonresponders
 Sample at the same time of day and from same route
 Identify the best control strain by examining the
literature
JAX® Mice |
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Tips for Working with Diabetic Mice
Smart experimental design
Actively minimize distress
o
o
o
o
What is distress?
Why should we care?
Experimental manipulations
Routine husbandry
JAX® Mice |
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Animals Strive to Adapt to Their
Environment
Distress
When the biological cost
of stress affects
biological function(s)
Recognition and Alleviation of Distress in Laboratory Animals (2008)
Institute for Laboratory Animal Research (ILAR)
JAX® Mice |
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Extreme Cold Causes Distress in
Mice
26-34oC
Comfort
Ability to maintain
homeostasis
Temperature
18-26oC
Stress
Extra resources
needed to maintain
homeostasis
<18oC
Distress
<0oC
Death
Resources depleted,
physiologic changes
occur to maintain
homeostasis
Adapted from: Gordon CJ (1993) New York: Cambridge University Press. xii: 276.
JAX® Mice |
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Diabetic Phenotypes are Sensitive
to Distress
Cage Shelf Level Effects
Type 1 Diabetes latency
relative to cage shelf level
Top Shelf
Middle Shelf
Bottom Shelf
Top Shelf = 57” above
floor
Bottom Shelf = 6.75”
above floor
Ader D. et al. 1991. Psychosomatic Medicine 53: 313-21. PMID:1882012
JAX® Mice |
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Diabetic Phenotypes are Sensitive
to Distress
Cage Shelf Level Effects
Type 1 Diabetes latency
relative to cage shelf level
Top Shelf
Top Shelf = 57” above
floor
Middle Shelf
Bottom Shelf = 6.75”
above floor
Bottom Shelf
Female NOD mice housed
on the top shelf take
longer to develop type 1
diabetes
Ader D. et al. 1991. Psychosomatic Medicine 53: 313-21. PMID:1882012
JAX® Mice |
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Diabetic Phenotypes are Sensitive to Distress
Drug Delivery Effects
Efficacy of Rosiglitazone treatment by oral gavage in NONcNZO10/LtJ (004456)
-7
Study Day
1
2
3
4
5
6
7
8
9
10
11
Vehicle
Study Oral Gavage
Start Vehicle Dosing
12
13
14
15
16
17
Drug
Oral Gavage
Drug Dosing
In Vivo Pharmacology Services |
Study End
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Diabetic Phenotypes are Sensitive to Distress
Drug Delivery Effects
Efficacy of Rosiglitazone treatment by oral gavage in NONcNZO10/LtJ (004456)
-7
Study Day
1
2
3
4
5
6
7
8
9
10
11
Vehicle
12
13
14
Blood Glucose (mg/dl)
16
17
Drug
Study Oral Gavage
Oral Gavage
Start Vehicle Dosing
Drug Dosing
Fed Blood Glucose Values by Procedure Day
500
15
Study End
Glucose, Days -7, 1, & 10
400
300
200
100
0
NONcNZO10/LtJ
B6.V-Lepob/J
BKS.Cg-m +/+ Lepdb/J
In Vivo Pharmacology Services |
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Diabetic Phenotypes are Sensitive to Distress
Drug Delivery Effects
Efficacy of Rosiglitazone treatment by oral gavage in NONcNZO10/LtJ (004456)
-7
Study Day
1
2
3
4
5
6
7
8
9
10
11
Vehicle
Study Oral Gavage
Start Vehicle Dosing
12
13
14
15
16
17
Drug
Oral Gavage
Drug Dosing
Study End
Oral Glucose Tolerance Test
In Vivo Pharmacology Services |
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Diabetic Phenotypes are Sensitive to Distress
Drug Delivery Effects
Efficacy of Rosiglitazone treatment by oral gavage in NONcNZO10/LtJ (004456)
-7
Study Day
1
2
3
4
5
6
7
8
9
10
11
Vehicle
Study Oral Gavage
Start Vehicle Dosing
12
13
14
15
16
17
Drug
Oral Gavage
Drug Dosing
Study End
Oral Glucose Tolerance Test
Oral gavage dosing of
Rosiglitazone has no effect on
glucose tolerance
In Vivo Pharmacology Services |
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Diabetic Phenotypes are Sensitive to Distress
Drug Delivery Effects
Efficacy of Rosiglitazone treatment by oral gavage in NONcNZO10/LtJ (004456)
Pan HJ et al. 2005. Diabetes 54(6):1854-62. PMID:15919809
In Vivo Pharmacology Services |
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Diabetic Phenotypes are Sensitive to Distress
Drug Delivery Effects
Efficacy of Rosiglitazone treatment by oral gavage in NONcNZO10/LtJ (004456)
Rosiglitazone delivered in grain
significantly reduces blood
glucose levels
Pan HJ et al. 2005. Diabetes 54(6):1854-62. PMID:15919809
In Vivo Pharmacology Services |
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Experimental Manipulations
Acclimate mice
o Allow 1-2 weeks for acclimation
Look for study induced distress
o Compound administration
(e.g. oral gavage or interperitoneal
delivery)
Keep thorough records
o Cage shelf level
Sample consistently
o Same time of day, from same site (tail or saphenous vein)
Include extra mice
o To account for non-responders/outliers
JAX® Mice |
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Routine Husbandry:
Room Health Status
Some strains require specific health
status for phenotypes to develop
Diabetes development in NOD/ShiLtJ
(001976) mice is reduced by exposure
to pathogens – SPF housing
recommended
King S et al. 2011. PLoS One 6: e17049 PMID:21364875
JAX® Mice |
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Routine Husbandry:
Housing Configuration
Group Housing
Pros
Cons
Cost effective
Risk of fighting
Social interaction
Experimental
limitations
Warmth
When is reduced cage density
housing recommended
Never group
house mice from
different shipping
containers!
Long term experiments (>3 months)
To alleviate fighting
Wound healing experiments
Institutional policies
JAX® Mice |
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Routine Husbandry:
Physical Cage Conditions
Cage Bedding Considerations
Do increase the amount of bedding for obese strains
Do consider using cellulose based bedding such as
ALPHA-Dri® for superior absorbency and ammonia
control (polyuric strains)
Do not use corn cob bedding for obese strains
Enrichment
Minimize distress and promote normal behaviors
o
o
Reduce aggression
Relieve boredom
Options:
o
o
o
Plastic Mouse Houses or Igloos
Soft fibrous nesting material
Nylabones®
JAX® Mice |
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Routine Husbandry:
Food and Water
Food Considerations – Type 2 Diabetes Models
Maintain on same high fat diet
Place small amount of food in bottom of cage encourage weight gain
Prevent food spoilage by completely replacing food with each cage
change
Water Considerations
If using automatic watering racks provide water bottles during
acclimation period
Check water frequently to ensure sufficient supply
JAX® Mice |
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Routine Husbandry:
Optimal Room Conditions
Choose quiet place
o Avoid noise and vibrations
House on lowest cage level
Minimal & consistent handling
Use clean forceps or gloves
Temperature
Light cycle and intensity
www.jax.org/jaxmice/support/husbandry/room-conditions
JAX® Mice |
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Checklist to Minimize Distress
 Diabetic phenotypes are highly sensitive to distress
 Carefully choose health status of room
 Ensure the mouse colony environment is appropriate
o
o
Cage level, bedding, enrichment, food & water
Thoughtful handling
JAX® Mice |
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Thank you!
In need of mouse breeding and colony
management expertise to advance your
research?
Contact your regional representative today
www.jax.org/jaxmice/support/regionalcontacts
Contact technical support
www.jax.org/jaxmice/support/techsupport-index
JAX® Mice, Clinical & Research Services
1-800-422-6423 • 1-207-288-5845
[email protected] • www.jax.org/jaxmice
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