Rodents:
Mice
Dr. N. Matthew Ellinwood, D.V.M., Ph.D.
Spring 2012
IOWA STATE UNIVERSITY
COLLEGE OF AGRICULTURE AND LIFE SCIENCES
Taxonomy
•Kingdom: Animalia
•Phylum: Chordata
•Class: Mammalia
•Order: Rodentia
•Superfamily: Muroidea
• Family: Muridae
• Subfamily: Murinae
• Genus: Mus
•Species: musculus (house mouse)
Non-domestic “House Mouse”
• Mus musculus domesticus
– House mouse
– A domesticated opportunist
• Other mice may live in houses
– Mice coming in from woods/fields
• North American white-footed mice
Mice in Popular/Children’s
Literature
Ancient Origins and Modern
Retellings
• Aesop’s Fables
– The Lion and the
Mouse
– The Mouse, The
Frog, and the Hawk
– The Town Mouse and
the Country Mouse
• Beatrix Potter
The Antiquity of Cat and Mouse
Origins
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South Asia/Northern India
Spread to Mediterranean basin by 10,000 YBP
Europe by 3,000 YBP
Kept as pets in China (3,000 YBP)
Now found world wide (exclusive of Antarctica?)
Mice in human migrations
– Danish incursions to Madeira?
– Viking incursions previously unknown
– All mice in Madeira have a single mitochondrial linage
related to Scandinavia/Northern Germany
Modern Domestic Mice
• Chinese lexicon discussing “spotted mice”
– 1100 BCE
• Dancing mice (later descriptions of waltzing)
– Confucius, 500 BCE
• Japan
– Literature on various lines and breeding practices
• Japanese lines introduced to Europe early 1600s
• National Mouse Club, Britain, 1895
Natural History
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Life span: 1.5 years (extreme cases to 2+ yr)
Sexual maturity: 50-60 days
Estrous; 4-5 days
Weaning; 3-4 weeks
Pups; 4-12 per litter
Will tend to territoriality
– Manage as littermate/pairings
– Not ideally kept in groups
Reproduction and Growth
• Females, breed at 12 weeks
• Gestation – 21 days
• Cannibalism not uncommon
– Environmental changes and / or stresses
• Dams can be bred back at ~3 days
• Atricial young: Hair at 2-4 days, ears open
3-5 days, eyes open at 14 days
• Weaning at 3 weeks
• Remove males at 4 weeks
Territoriality and Pheromones and
Reproduction
• Vomeronasal organ (a distinct chemoreceptor organ
located in the nasal cavity; different neuronal
connections)
• Whitten effect
– W.K. Witten: male mouse pheromones will synchronize the
estrous cycle of group housed females
• Bruce effect
– Exposure of a bred or pregnant female to a new male will cause
pregnancy failure
• Vanderbergh effect
– Exposure to male urine pheromones will induce earlier first
estrus in prepubertal females
Housing
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Classic shoe box housing
Rodent chow
Slotted cage top feeder
Drip bottle water
– Draining/drowning
• Bedding
• 30-70% Humidity
• 65-85 oF
Feeding
• Rodent Chow
• Chewing
– Tooth health
– Enrichment
• Supplement sparingly
– Grains, seeds, vegetables
• Coprophagic
Behavior
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Primarily nocturnal
Little to no color vision
Acute hearing up to ultrasound range
Vocal communication in human hearing
(longer distance) and ultrasound range
(shorter distance)
Reproduction
• Male courting and mounting behavior
coincidental with ultrasound calling
– Can be induced by female urine
• Breeding at night
• Vaginal plug (gelatinous plug resulting
from seminal fluids)
• Gestation: 21 days
• Weaning at 3-8 weeks
Housing
• Trio Breeding
– Male X 2 females per cage
– Nesting material
– Females will often assist in raising young
• Housing males
– Co-housing possible if brothers
– Difficult to remove and reintroduce
• Male vs females as pet
– Males more exploratory
– Female urine lacks strong smell
Fancy Variants
• Rat and Mouse Club of America
– http://www.rmca.org/
• American Fancy Rat and Mouse Association
– http://www.afrma.org/
Modern Domestic Mice
• Mix of various types:
– Mus musculus musculus (eastern Europe)
– Mus musculus domesticus (western Europe), Mus
musculus castaneus (Southeast Asia)
– Mus musculus molossinus (Japan)
• Early important model of genetics
– First mammalian demonstration of Mendelian genetics
• Lucien Cuenot, 1902
– Early researchers
• William Castle and student, C.C. Little
– Little worked with and used stocks from A Lathrop
Fancy to Research
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Miss Abbie E.C. Lathrop
Illinois native
Producer pet trade, Granby, Mass.
Japanese waltzing mice
Began supplying research trade
Started developing inbred strains in 1910
– Same time as Little
– Published on mouse tumors with Leo Loeb of U. of Penn
• Died in 1918
Research History
• C line descend from Lathrop stock
• Females 57 and 58 mated to male 52
• Developed as
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C57BL
C57BR
Etc
Clarence Cook Little and the Jackson Laboratory
Jackson Laboratory
Jackson Laboratory
• Clarence Cook Little
– Cold Spring Harbor
– University of Maine (Agricultural Experiment
Station)
• Collection moved to Jackson Laboratory
– Housed mammalian genetic research and
cancer research
• Founded by Prexy and funded by wealthy
Detroit industrialists
Reproduction and Genetic
Malleability
• Mice/rodents
– Transgenic and knockout technology
• Short generation time
• Tolerated inbreeding
Mouse Strains
• Now over three thousand strains of mice
• Outbred stocks
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Closed stock
Min inbreeding (1% per generation)
Random matings of 25 pairs
Ex: NIH Swiss mice
• Heterogenous stocks
Inbred Lines
• 20 successive brother sister matings
Congenic
• Identical to a parental strain
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Exception will be at one locus
B6.129S6-Naglutm1Efn/J
Versus
C57BL/6J
Manipulated Genome
Transgenics
Transgenic: Techniques
Applications
Homologous Recombination:
(AKA Knockouts)
Knockout Techniques
Knockout Techniques
Knockout Application
• ALS
• SOD1 mouse
Knockins
Conditional Knockouts
• Cre Recombinase expressing mice
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Express ubiquitously
Express at developmental stages
Express in specific tissues/cells
Expression that is inducible
• Enzyme that cuts out a specific DNA sequence
– Lox P sites
– Floxed DNA sites of gene of interest
• Crosses lead to gene/function elimination
– Chromosomal excision