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Mapping ecologically relevant social behaviours by gene knockout in wild mice

2014; Nature Portfolio; Volume: 5; Issue: 1 Linguagem: Inglês

10.1038/ncomms5569

2041-1723

Lea Chalfin, Molly Dayan, Dana Rubi Levy, Steven N. Austad, Richard A. Miller, Fuad A. Iraqi, Catherine Dulac, Tali Kimchi,

Genetics and Physical Performance

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. Mice are important animal models for human disease research, however artificially selected laboratory mice may be unsuitable for studies of adaptive behavioural response. Here, the authors backcross wild mice with mutant laboratory mice and uncover behavioural gene functions unique to wild mice, thereby offering an improved model for studying human traits.