GENETIC-MAPPING OF A LOCUS (MASS1) CAUSING AUDIOGENIC-SEIZURES IN MICE

Frings audiogenic seizure-susceptible mice are a model for sensory-evo ked reflex seizures. Their seizure phenotype is characterized by wild running, loss of righting reflex, tonic flexion, and tonic extension i n response to high-intensity sound stimulation. The Frings mice repres ent an inbred colony that has not been genetically characterized, This investigation studied the mode of inheritance for audiogenic seizures by crossing the Frings mouse with the seizure-resistant C57BL/6J mous e. Among the backcross progeny generated by crossing (Frings x C57BL/6 J)F1 mice with the Frings strain, 391 of the 836 N2 progeny were audio genic seizure susceptible, a finding consistent with monogenic inherit ance. Genetic mapping and linkage analysis of hybrid mice using MIT mi crosatellite marker sequences localized the seizure gene, named mass1 for monogenic audiogenic seizure susceptible, to an approximately 3.6 cM interval in the middle of mouse chromosome 13. Linkage of mass1 to chromosome 13 is an important step in identifying the gene associated with a monogenic seizure disorder in mice, which may ultimately lead t o a better understanding of the pathophysiology of human seizure disor ders. (C) 1998 Academic Press.