Issues in the search for candidate genes in mice as potential animal models of human aggression

Conceptual and methodological issues in the search for candidate genes for mouse aggression and for the development of animal models of human aggression are considered. First, the focus is on genetic and then behavioural aspects of the search for candidate genes in mice. For the genetic aspect, two approaches are presented. In mice, these are chromosome mapping of polymorphic genes and evaluation of gene (polymorphic or monomorphic) function using knockout mutants. For the behavioural aspect, several parameters, including the type of aggression, measure of aggression, test situation and opponent type can have effects on the obtained genetics. This is illustrated for the offence type of attack behaviour in mice. The current combination of sophisticated genetic and behavioural analyses will result in time in the identification of many of the genes with effects on variation and development of one or more types of murine aggression. Since mouse and humans have many homologous genes mapped to homologous chromosome regions, it is conceivable that individual genes identified for one or more types of mouse aggression may be developed as animal models for human aggression. Genetic, physiological and behavioural limitations and uses of such models are discussed.