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Linkage of strain-specific nicotinic receptor α7 subunit restriction fragment length polymorphisms with levels of α-bungarotoxin binding in brain

1996; Elsevier BV; Volume: 43; Issue: 1-2 Linguagem: Inglês

10.1016/s0169-328x(96)00149-0

1872-6941

Jerry A. Stitzel, Douglas A. Farnham, Allan C. Collins,

Marine Toxins and Detection Methods

Inbred mouse strains have been shown to differ in their levels of brain α-bungarotoxin binding. These differences in α-bungarotoxin receptors have been shown to correlate with an animal's sensitivity to nicotine-induced seizures. Recent studies have shown that the α7 nicotinic acetylcholine receptor subunit is the major α-bungarotoxin binding site in rodent brain. In this report, we examined whether mouse strains that differ in levels of α-bungarotoxin binding and sensitivity to nicotine-induced convulsions also differ for the α7 subunit. A full-length murine α7 cDNA was cloned and sequenced and found to be identical to that of a mouse α7 cDNA recently reported. Subsequently, a comparison of α7 cDNA sequences and RNA species was performed between two strains (C3H/2 and DBA/2) that differ in levels of brain α-bungarotoxin binding and sensitivity to nicotine-induced seizures. The only difference observed was a single nucleotide difference in the open reading frame of α7 that does not affect the primary amino acid sequence. Inbred strains were also surveyed for restriction fragment length polymorphisms at the α7 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 α7 genotype and α-bungarotoxin receptor levels. A significant association between genotype and receptor levels was observed in both the F2 and backcross generations. These results indicate that α7 genotype is an important determinant of α-bungarotoxin receptor levels.