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

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 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 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 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 Supplement sparingly Coprophagic Tooth health Enrichment Supplement sparingly Grains, seeds, vegetables Coprophagic

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)

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 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

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 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 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 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 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 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