Rapid selection response for contextual fear conditioning in a cross between C57BL/6J and A/J: behavioral, QTL and gene expression analysis.

We used short-term selection to produce outbred mouse lines with differences in contextual fear conditioning. Within two generations of selection all low selected mice were homozygous for the recessive tyrc allele and showed the corresponding albino coat color. Freezing differed in the high and low selected lines across a range of parameters. We identified several QTLs for the selection response, including a highly significant QTL at the tyr locus (p < 9.6−10). To determine whether the tyrc allele was directly responsible for the response to selection, we examined B6 mice that have a mutant tyr allele (tyrc−2j−) and an AJ congenic strain that has the wild-type B6 allele for tyr. These studies showed that the tyr allele had a small influence on fear learning. We used Affymetrix microarrays to identify many differentially expressed genes in the amygdala and hippocampus of the selected lines. We conclude that tyr is one of many alleles that influence fear conditioning.