Nonallelism for the Audiogenic Seizure Prone (ASP1) and the Aryl Hydrocarbon Receptor (AHR) Loci in Mice

Abstract

Previous studies showed an association between the Ahr locus on Chr 12 and a maj or gene, Aspl, that influences susceptibility to audiogenic seizures (AGS) in mice. Although the association was thought to involve close linkage, a pleiotropic effect of the Ahr locus on AGS susceptibility was not excluded. Two congenic strains, D2.B6N-Aspl^b and the D2N.B6N-Ahr^bl, were used to evaluate further the association between the Ahr and Aspl loci. Both strains are genetically identical to the AGS susceptible DBA/2 (D2) strain except for a small amount of C57BL/6N (B6N) genome surrounding the Ahr locus and encompassing the Aspl locus. The AGS susceptibility of both congenic strains is similar and significantly lower than that of the D2 strain. We found that the Ahr/Aspl critical region encompasses 5.5–7.0 cM from the proximal microsatellite marker D12Mit153 to the distal marker D12Mit112. The D2N.B6N-Ahr^bl expresses B6 alleles for all markers within the critical region, whereas the D2.B6N-Aspl^h expresses the B6 aliele only at the Aspl locus. Furthermore, we determined that the D2.B6N-Aspl^b mouse expresses both the D2 phe-notype and genotype at the Ahr locus, i.e., zoxazolamine paralysis and T to C and G to A transition mutations in the Ahr cDNA at bp sites 3330 and 3336, respectively. We therefore conclude that the Ahr and Aspl loci are nonallelic and that the Ahr gene is excluded as a candidate for Aspl.

Key Words:

• Epilepsy
• convulsion
• gene mapping
• positional cloning
• multifactorial inheritance

Additional information

Notes on contributors

Thomas N. Seyfried

Joyce Laing works in the Department of Child and Family Psychiatry, Playfield House, Cupar, Fife, and is a Consultant Art Therapist to Psychiatric Hospitals and Prisons and Chairwoman of the Scottish Society of Art and Psychology.