1. College of Agriculture and Life Sciences
Rodents: Mice
Dr. N. Matthew Ellinwood, D.V.M., Ph.D.
Spring 2012
Iowa State University
College of Agriculture and Life Sciences

2. Taxonomy Kingdom: Animalia Phylum: Chordata Class: Mammalia
Order: Rodentia
Superfamily: Muroidea
Family: Muridae
Subfamily: Murinae
Genus: Mus
Species: musculus (house mouse)

3. 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

4. Mice in Popular/Children’s Literature

5. 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

6. The Antiquity of Cat and Mouse

7. Origins 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

8. 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

9. Natural History Life span: 1.5 years (extreme cases to 2+ yr)
Sexual maturity: 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

10. 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

11. 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

12. Housing Classic shoe box housing Rodent chow Slotted cage top feeder
Drip bottle water
Draining/drowning
Bedding
30-70% Humidity
65-85 oF

13. Feeding Rodent Chow Chewing Supplement sparingly Coprophagic
Tooth health
Enrichment
Supplement sparingly
Grains, seeds, vegetables
Coprophagic

14. Behavior 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)

15. 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

16. Housing Trio Breeding Housing males Male vs females as pet
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

17. Fancy Variants Rat and Mouse Club of America
American Fancy Rat and Mouse Association

18. 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

19. Fancy to Research 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

20. Research History C line descend from Lathrop stock
Females 57 and 58 mated to male 52
Developed as
C57BL
C57BR
Etc
Clarence Cook Little and the Jackson Laboratory

21. Jackson Laboratory

22. 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

24. Reproduction and Genetic Malleability
Mice/rodents
Transgenic and knockout technology
Short generation time
Tolerated inbreeding

25. Mouse Strains Now over three thousand strains of mice Outbred stocks
Closed stock
Min inbreeding (1% per generation)
Random matings of 25 pairs
Ex: NIH Swiss mice
Heterogenous stocks

26. Inbred Lines
20 successive brother sister matings

27. Congenic Identical to a parental strain Exception will be at one locus
B6.129S6-Naglutm1Efn/J
Versus
C57BL/6J

28. Manipulated Genome

29. Transgenics

30. Transgenic: Techniques Applications

31. Homologous Recombination: (AKA Knockouts)

32. Knockout Techniques

33. Knockout Techniques

34. Knockout Application
ALS
SOD1 mouse

35. Knockins

36. Conditional Knockouts
Cre Recombinase expressing mice
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