Rodent biology
Timo Nevalainen
University of Eastern Finland
Kuopio, Finland
1
Origin
Mouse


house mouse (Mus musculus)
use started 1600’s, but increased during
1800’s with increasing research activity
Rat


Brown rat (Rattus norvegicus) came from Asia
to Europe at the beginning of 1700’s
Black rat (Rattus rattus) has faded away
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Quiz: Rat or mouse?
Quiz: Roof rat or Brown rat?
3
Why chosen ?
Synonyms of disease and death, not
connected to biomedical research
Small, economical and mammal
Easily adapted and tamed
Several common features with other
mammals
4
Reproduction
Mouse
Rat
Sexual maturity 6-8 weeks
6-8 weeks
Estrus cycle
4-5 days
4-5 days
Gestation
19-21 days
19-23 days
Weaning
3 weeks
3 weeks
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Development of vertebrate
embryos
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Life cycle of mouse
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8
9
10
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Animal age vs. human age
Comparing rat’s to human’s age: How old
is my rat in people years?
Aging in Mouse and Human Systems: A
Comparative Study
AnAge Database
Translating time - across developing
mammalian brains
13
Vital Statistics
Mice:
Rats:
Heart rate = 306-700
beats/minute
Respiratory rate =
85-200
breaths/minute
Body temperature =
36.5 C
Heart rate = 250 –
450 beats/minute
Respiratory rate =
70-115
breaths/minute
Body temperature =
36.5 C
14
Strains and Stocks
Inbred - developed out of brothersister mating for 20 generations,
producing 99% genetic homology.
Outbred stocks (random bred) are
genetically heterozygous.
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White rat?
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Stock or strain ?
Wistar (albino), Sprague-Dawley (albino),
Long-Evans origin (origin)
Outbreds are stocks
Inbred and other defined animals are
strains
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Most common inbred mouse
strains and correct name
AKR
BALB/c
C3H
C57BL
C57BL/10
C57BL/6
DBA/2
NZB
AK
C
C3
B
B10
B6
D2
ZB
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Albinos, so what ?
c-locus albinism – melanin is missing
Melanocytes present, but because of
absence of tyrosinase; no melanin is
produced
Albinism results in changes of
neuroanatomy, -physiology, metabolism
and behavior
Creel. Pharmacology, Biochemistry and
Behaviour 12:969-977, 1980
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Rat's vision
Human, normal vision
red-insensitive colorblind, faint color
Normally-pigmented rats have blurry dichromatic vision
with low color saturation
Albino rats may see a very blurry, light-flooded world
On a bright day, albino rats may be completely dazzled
21
Albinism and vision
Albino rats can have retinal degeneration
at low light intensities
More than 60 lux for 30 weeks in cage –
albino rats are likely to be blind
Manage with other senses
Animal room light mainly for people,
animals must be protected from excessive
light
22
What do rats see?
www.ratbehavior.org/images/HumanCam.mov
www.ratbehavior.org/images/RatCam.mov
www.ratbehavior.org/images/AlbinoRatCam.mov
23
Coprophagy
rats and mice eat their own feces
Important for vitamin
Directly from anus – grid floor does not
prevent
Preventing coprophagy decreases growth
by 10-20%
Important in pharmacology with per os
administration
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Full article
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Thermoregulation
No sweat glands



Cannot dissipate heat by sweating or panting
In extreme situation moist fur with saliva – can
lead to dehydration
Poor heat tolerance
Usually change amount of circulation to
hairless areas - tail
29
Rat tail anatomy
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Diurnal rhythm
Rats and mice are nocturnal animals
Activity and eating during dark
Daytime mainly sleep
In research please note


Many hormones fluctuate considerably
according to time
If want to study during activity, reverse the
light cycle
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Metabolism and Body Scaling
Concept of METABOLIC
SIZE.
Mice and rats have high
surface area to body
volume ratios.
Volume:
Low
High
Surface Area:
High
Low
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Relationships of Metabolic Size
High surface area:
Low surface area:
Dissipate body heat
Conserve body heat
Compensate with
increase of Metabolic
Rate
Compensate with
decrease in Metabolic
Rate
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Consequences from Metabolic Size:
Scaling drug doses between species of
different size (apart from species specific
features).

Higher dose rates (mg/kg) in mice, rats than in
larger species.
 To use the “dog dose rate”
in mice – risk of inefficacy.
 To use the “mouse dose
rate” in dogs – risk of
toxicity.
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Do we house rodents right?
Care routines aim at hygiene

cage used to be an open space
Other things may be important to
animals


Digging, nest making, gnawing
In open cage – walling effect
The more space – the better ?
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Do we feed rodents correctly ?
same chow for both rats and mice
same diet for breeding and maintenance
routine method = ad libitum




eat too much
become obese
shorter life span
more tumors
group housing and restricted feeding are
not compatible
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Environmental
Enrichment
Lab strains of rats and mice kept under
field conditions express wild rodent
behaviors.
Environmental enrichment – prefer nest
boxes, nest material and gnawing
materials.
Effect of environmental enrichment on
animals: exposure to complex experiences
alter neuroanatomical parameters and
chemistry associated with memory and
learning. Animals exhibit greater
adaptability.
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Rodent autopsy/anatomy websites
Pathology and Autopsy of a Mouse
3D MRI Digital Atlas Database of Adult C57BL/6J Mouse Brain
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Anatomy information on mouse
www.ana.ed.ac.uk/anatomy/database/
www.informatics.jax.org/mgihome/GXD/gxdgen.shtml
http://genex.hgu.mrc.ac.uk/Databases/Anatomy/new/home.shtml
www.rodentia.com/wmc/domain_mouse.html
www.hms.harvard.edu/research/brain/
www.hms.harvard.edu/research/brain/
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http://wholebraincatalog.org/
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Anatomy
Harderian gland (lacrimal) –



Tears contain porphyrin
Normal function of lubrication
Conditions of stress (non-specific)
cause excess accumulation around
eyes and nose.
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Teeth Overgrowth
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Gastrointestinal System
Similarities:
Stomach – glandular & aglandular regions
Large cecum
Pancreas diffuse
Differences
Rat – no gall bladder
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Urinary
Urine :
Mouse - 4X concentrated as man
Rat – 2X concentrated as man
Excrete urine 1-2 drops at a time.
Pass urine when picked up – easy to collect a
urine sample.
Urine rich in proteins
Allergenic!
Exposure via dusts, contact with skin
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Pheromones
present in male mice urine
effects on reproduction



Lee-Boot effect: Females without males
– estrus cycles is suppressed
Whitten effect: Male to a female group –
estrus cycle synchronized
Bruce effect: Strange male into female
group within 24h from mating –
implantation prevented
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Estrus Detection
Both of these mice
are in estrus – they
are in different
stages.


The mouse on the
top would be chosen
for an immediate
breeding pair set up.
The mouse on the
bottom is in an earlier
stage of estrus.
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Estrus Detection
Estrus
Note the swollen, moist
and open appearance to the
mucus
vaginal opening; coloration
of mucus membranes is pale.
Non-Estrus
Note the closed vaginal
opening and pale
membrane color.
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Estrus vs. Non-Estrus
* swollen vaginal tissue
* gaping vaginal opening
* moist tissues
* bright pink/purple
mucus membranes
* no swelling evident
* closed vaginal opening
* dry tissues
* pale mucus membranes
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Copulatory Plugs In Mice
The copulatory plug (most often referred
to as the vaginal plug), is made of
several different components---sperm,
ejaculate fluids, and mucus are primary
substances that harden within the
cervix.
The plug forms following copulation and
is visible within, or slightly protruding
from, the vaginal opening. Its presence
indicates a successful mating – but
does not guarantee that conception has
occurred.
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Checking for Plugs
Checking females
for plugs is best
done in the early
morning (before
9:00 a.m.) if the
animals are housed
under a typical
12/12 light cycle.
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Checking for Plugs
The plug is opaque,
whitish, and has a
waxy consistency. It is
generally easy to
identify while still
within the vaginal
opening.
It may also be identified in the bedding as a large waxy
“chunk,” if one checks closely. Generally, plugs are
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expelled close to the nest/sleep area.
Checking for Plugs
Sometimes
the plug is
difficult to
visualize in
situ. To aid with
its identification,
one can gently
palpate the area to help distend and partially expel the plug.
The use of forceps is not recommended. Extreme care must
be taken if forceps are used, and the plug should never
be removed.
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Rodent Pup Sexing
Sexing young rodents can be challenging – but
with practice, pups as young as day 3 can be
consistently identified.



Males have twice the anogenital distance that
females have.
The nipple line in females is identifiable as early as
day 8 or 9.
Once hair is present ~D9, the area between the
testicles and anus is completely grown over with hair;
in females the area is defined as a hairless line
between the vaginal opening and anus.
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Day 5
Male
Female
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Day 7
Female
Male
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Day 12
Male-right –
note the hair
growth between
the anus and
prepuce
Female-left –
note the visible
line between
the
vaginal opening
and the anus,
note the nipple
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line.
Day 21
Female-left
Male-right
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Adult
Female
Note “line” between anogenital area
is clearly visible; nipples are easily
identified.
Male
Note anogenital area
is completely fur covered.
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Adults
Sexing Rodents
Anogenital distance is twice
as great in the male
Female
Male
Inguinal canal remains open
in rodent males; testicles
retract to abdomen.
4 weeks
Male
Female
Anogenital distance:
the space between anus
and genital papilla
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Otoscopic method - rat
Scand J Lab Anim Sci 25: 5-9, 1998
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Material in the web
Rat behavior

www.ratlife.org
Rat Behavior and Biology

www.ratbehavior.org
Assessing the Health and Welfare of Laboratory Animals

http://www.ahwla.org.uk/
Laboratory Animal Medicine and Management

www.ivis.org
Vaginal smears in the rat
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Books

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The Laboratory Mouse. Hedrich H & Bullock G (eds).
Elsevier 2004.
The Laboratory Rat. Krinke GJ (ed). Academic Press 2000.
Suckou MA, Danneman P, Brayton C. The Laboratory
Mouse. CRC Press 2001.
Sharp PE, LaRegina MC. The Laboratory Rat. CRC Press
1998.
Popesko, Rajtová, Horák; A color atlas of anatomy of small
laboratory animals; Volume one and two; Wolfe Publishing
Ltd,1992
T.Iwaki, H.Yamashita, T .Hayakawa; A color atlas of
sectional anatomy of the mouse. Braintree Scientific, 2001
T. HAYAKAWA, T. IWAKI A Color Atlas of Sectional
Anatomy of the Rat
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Reference material
Training in Basic Biomethodology for
Laboratory Mice

for free single copy -> rodentcd@od.nih.gov
Basic Biomethodology for Laboratory Rats

rats_cd@mail.nih.gov
Training in Survival Rodent Surgery

for free single copy -> rodent-cd@mail.nih.gov
Waynforth & Flecknell. Experimental and
surgical technique in the rat. 2nd edition.
Academic Press. 1994
Pathology of laboratory animals - AFIP
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