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.

How does sex matter? Behavior, stress and animal models of neurobehavioral disorders

“…In this connection, the sex bias in the domestication process resulted in the loss of intrasexual aggression, reproductive competition and exploratory behaviors mostly in females of laboratory strains. This implies that domestication processes may have impacted females more than males and eroded many behavioral traits of ancestral wild female mice, as also reported in a recent study by Chalfin et al (2014).…”

Social propinquity in rodents as measured by tube cooccupancy differs between inbred and outbred genotypes

“…It is also clear that inbred mice can differentiate between familiars and strangers, because social phenomena such as emotional contagion have been shown to be more pronounced between C57BL/ 6 cagemates than between strangers (21). Dramatic phenotypic (especially stress-related) and gene expression differences between mutants placed on C57BL/6 ("domesticated") versus rederived wild mice have been reported recently (14).…”

“…Laboratory mouse strains are poor representatives of the species in at least three ways: (i) they are genetically homozygous at every locus; (ii) they have been artificially selected for both tameness and reproductive success under laboratory conditions; and (iii) postweaning same-sex housing deprives them of an ethologically relevant social environment. Robust differences in stress and social behaviors between inbred mice and wild mice have been reported (12)(13)(14). We thus evaluated TCOT behavior in outbred, inbred, and wild-derived mice.…”

Assortative mating among animals of captive and wild origin following experimental conservation releases

“…Third, any other phenotypic difference (e.g. variation in daily activity schedules or microhabitat use) arising between captive and wild parents that reduced mating opportunities post-release could further limit frequency of mixed-origin mating [18].…”