Rodents: Mice

1. 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: 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

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 • 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 • 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 • http://www.rmca.org/ • American Fancy Rat and Mouse Association • http://www.afrma.org/

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: TechniquesApplications

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