Classical genetic analysis of GABA-related seizures.
Differences in resistance to 3-mercaptopropionic acid (MP)-induced seizures exist between DBA/2Ibg and C57BL/6Ibg inbred strains of mice; C57BL/6Ibg mice are more resistant to MP-induced seizures. To determine the mode of inheritance for seizure resistance, a classical genetic analysis was conducted using these two parental strains, their F1, F2, and backcross generations. Latencies to seizure onset and tonus after intraperitoneal (IP) injections of MP (25-40 mg/kg) were quantified. For all populations mean latencies to onset and tonus decreased in a dose dependent manner with the hybrid generations exhibiting a seizure resistant phenotype resembling the C57BL/6Ibg strain. In general, female mice were less resistant to MP-induced seizures than males; however, a significant degree of resistance was retained by the C57BL/6Ibg females and their female progeny. A quantitative assessment of the pattern of inheritance for seizure resistance using a weighted least-squares regression approach indicated that an additive-dominance model explained latency to seizure onset data at 25, 35 and 40 mg/kg. However, at 30 mg/kg, the model required the addition of an epistatic parameter to best describe mean scores at this dose. The results of these analyses suggest that resistance to MP-induced seizures is transmitted in a dominant manner.
Martin
B J
BJ
Department of Psychology, University of Colorado, Boulder 80309.
Marley
R J
RJ
Miner
L L
LL
Wehner
J M
JM
D015097:3-Mercaptopropionic Acid; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D005799:Genes, Dominant; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012640:Seizures / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D012737:Sex Factors; D013045:Species Specificity; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D005680:gamma-Aminobutyric Acid; D015097:3-Mercaptopropionic Acid