Mapping ecologically relevant social behaviours by gene knockout in wild mice

Nat Commun. 2014 Aug 5;5:4569. doi: 10.1038/ncomms5569.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal*
  • Crosses, Genetic
  • Female
  • Gene Knockout Techniques
  • Genotype
  • Hormones / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout*
  • Mutation
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Smell / genetics
  • Social Behavior
  • TRPC Cation Channels / genetics


  • Hormones
  • TRPC Cation Channels
  • Trpc2 protein, mouse