Linkage of strain-specific nicotinic receptor alpha 7 subunit restriction fragment length polymorphisms with levels of alpha-bungarotoxin binding in brain.

Inbred mouse strains have been shown to differ in their levels of brain alpha-bungarotoxin binding. These differences in alpha-bungarotoxin receptors have been shown to correlate with an animal's sensitivity to nicotine-induced seizures. Recent studies have shown that the alpha 7 nicotinic acetylcholine receptor subunit is the major alpha-bungarotoxin binding site in rodent brain. In this report, we examined whether mouse strains that differ in levels of alpha-bungarotoxin binding and sensitivity to nicotine-induced convulsions also differ for the alpha 7 subunit. A full-length murine alpha 7 cDNA was cloned and sequenced and found to be identical to that of a mouse alpha 7 cDNA recently reported. Subsequently, a comparison of alpha 7 cDNA sequences and RNA species was performed between two strains (C3H/2 and DBA/2) that differ in levels of brain alpha-bungarotoxin binding and sensitivity to nicotine-induced seizures. The only difference observed was a single nucleotide difference in the open reading frame of alpha 7 that does not affect the primary amino acid sequence. Inbred strains were also surveyed for restriction fragment length polymorphisms at the alpha 7 locus. Strain-specific polymorphisms were identified, and F2 and backcross animals from a classic genetic cross between C3H/2 and DBA/2 mice were compared for the inheritance of alpha 7 genotype and alpha-bungarotoxin receptor levels. A significant association between genotype and receptor levels was observed in both, the F2 and backcross generations. These results indicate that alpha 7 genotype is an important determinant of alpha-bungarotoxin receptor levels.