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 brai n 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-bungarot oxin 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 sequenc ed and found to be identical to that of a mouse alpha(7) cDNA recently reported. Subsequently, a comparison of alpha(7) cDNA sequences and R NA species was performed between two strains (C3H/2 and DBA/2) that di ffer in levels of brain or-bungarotoxin binding and sensitivity to nic otine-induced seizures. The only difference observed was a single nucl eotide difference in the open reading frame of alpha(7) that does not affect the primary amino acid sequence. Inbred strains were also surve yed for restriction fragment length polymorphisms at the alpha(7) locu s. Strain-specific polymorphisms were identified, and F-2 and backcros s animals from a classic genetic cross between C3H/2 and DBA/2 mice we re compared for the inheritance of alpha(7) genotype and alpha-bungaro toxin receptor levels. A significant association between genotype and receptor levels was observed in both the F-2 and backcross generations . These results indicate that <alpha(7) genotype is an important deter minant of alpha-bungarotoxin receptor levels.