title: Mapping ecologically relevant social behaviours by gene knockout in wild mice.
abstract: The laboratory mouse serves as an important model system for studying gene, brain and behavioural interactions. Powerful methods of gene targeting have helped to decipher gene-function associations in human diseases. Yet, the laboratory mouse, obtained after decades of human-driven artificial selection, inbreeding, and adaptation to captivity, is of limited use for the study of fitness-driven behavioural responses that characterize the ancestral wild house mouse. Here, we demonstrate that the backcrossing of wild mice with knockout mutant laboratory mice retrieves behavioural traits exhibited exclusively by the wild house mouse, thereby unmasking gene functions inaccessible in the domesticated mutant model. Furthermore, we show that domestication had a much greater impact on females than on males, erasing many behavioural traits of the ancestral wild female. Hence, compared with laboratory mice, wild-derived mutant mice constitute an improved model system to gain insights into neuronal mechanisms underlying normal and pathological sexually dimorphic social behaviours.
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Lea
authors.initials: L
authors.lastname: Chalfin
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Molly
authors.initials: M
authors.lastname: Dayan
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Dana Rubi
authors.initials: DR
authors.lastname: Levy
authors.affiliation: Department of Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294-1170, USA.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Austad
authors.affiliation: Department of Pathology and Geriatrics Center, University of Michigan School of Medicine, Ann Arbor, Michigan 48109-2200, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Miller
authors.affiliation: Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv Universiity, Tel-Aviv 69978, Israel.
authors.forename: Fuad A
authors.initials: FA
authors.lastname: Iraqi
authors.affiliation: Department of Molecular and Cellular Biology, Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts02138, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dulac
authors.affiliation: Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tali
authors.initials: T
authors.lastname: Kimchi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003433:Crosses, Genetic; D005260:Female; D055786:Gene Knockout Techniques; D005838:Genotype; D006728:Hormones / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012903:Smell / Q000235:genetics; D012919:Social Behavior; D050052:TRPC Cation Channels / Q000235:genetics
chemical_list: D006728:Hormones; D050052:TRPC Cation Channels; C491858:Trpc2 protein, mouse