Loss of aggression, after transfer onto a C57BL/6J background, in mice carrying a targeted disruption of the neuronal nitric oxide synthase gene

Phenotypic differences among mice with disrupted genes and those with wild- type alleles have not provided the necessary evidence for desired gene/phen otype correlations. These differences could be due to "passenger genes" fro m the donor 129 strains that are used to produce stem cells. Three variatio ns of attack behavior were measured, using mice carrying a disruption of th e neural nitric oxide synthase gene. In the first population, the disrupted gene had been maintained on a mixed background including C57BL/6J and 129 alleles. We have developed a second population in which the disrupted gene was transferred onto a C57BL/6J background during five backcross generation s. On the mixed C57BL/6J-129 background, mice homozygous for disrupted Nos1 alleles attacked more frequently, had shorter attack latencies, and presen ted a greater number of attacks than mice carrying nondisrupted alleles. On the C57BL/6J background, no significant difference persisted between the c arriers of the disrupted gene and their noncarrier siblings. The noncarrier s on the mixed C57BL/6J-129 background, and the carriers or noncarriers on the C57BL/6J background, did not differ from C57BL/6J. The frequency of att acking males was identical in the homozygous carriers of the disrupted gene , in the mixed C57BL/6J-129 background, and in the 129/SvPas, which approxi mates the 129/SvJae strain from which the stem cells were derived to produc e the disrupted Nos1 gene. These results suggest that Nos1 disruption was n ot implicated in attack behavior. A possible passenger-gene effect from the 129 donor strain is discussed.