Mapping ecologically relevant social behaviours by gene knockout in wild mice

Lea Chalfin, Molly Dayan, Dana Rubi Levy, Steven N. Austad, Richard A. Miller, Fuad A. Iraqi, Catherine Dulac and Tali Kimchi ()
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Lea Chalfin: Weizmann Institute of Science
Molly Dayan: Weizmann Institute of Science
Dana Rubi Levy: Weizmann Institute of Science
Steven N. Austad: University of Alabama at Birmingham
Richard A. Miller: University of Michigan School of Medicine
Fuad A. Iraqi: Sackler Faculty of Medicine
Catherine Dulac: Howard Hughes Medical Institute, Harvard University
Tali Kimchi: Weizmann Institute of Science

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5569

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