Genetic dissection of susceptibility to audiogenic seizures in inbred mice

Mice of some inbred strains, such as 21-day-old DBA/2J mice, have generalized convulsions when exposed to intense auditory stimulation. Analysis of susceptibility to audiogenic seizures in BXD recombinant inbred strains has demonstrated the influence of at least three loci. One locus, Asp-1, is located on chromosome 12 between Ah and D12Nyu1; another locus, Asp-2, is on chromosome 4, tightly linked to b. Here we report evidence that Asp-2 is located within an 8-centimorgan segment distal to b and that Asp-3 is linked to Mtv-1 on chromosome 7. We also present evidence that these three loci account for most of the heritable variation in susceptibility to audiogenic seizures in crosses of DBA/2J and C57BL/6J mice and that susceptibility to audiogenic seizures is influenced by genomic imprinting. Thus, genomic imprinting may complicate linkage and mapping studies and should be considered in analyses of complex modes of inheritance.