Chrna7 genotype is linked with alpha7 nicotinic receptor expression but not alpha7 RNA levels

Studies using the radio-labeled nicotinic receptor antagonist [I-125]-alpha-bungarotoxin, which binds to alpha 7 subunit containing nicotinic receptors, have demonstrated that mouse strains vary considerably in the number of alpha 7-containing nicotinic receptors in brain. In addition, brain region specific differences in alpha-bungarotoxin binding between the mouse strains C3H/Ibg and DBA/2 have been linked to polymorphisms in Chrna7, the gene that encodes the alpha 7 subunit. In the studies described here, we evaluated whether the relationship between Chrna7 genotype and individual differences in alpha-bungarotoxin binding levels in adult brain might be due to an effect of Chrna7 genotype on alpha 7 RNA levels. Quantitative autoradiography of coronal brain slices from F2 mice derived from the parental strains C3H/Ibg and DBA/2 demonstrate that Chrna7 genotype is not linked to alpha 7 RNA levels. In contrast, quantitative autoradiography confirmed the linkage of Chrna7 genotype with alpha-bungarotoxin binding levels in hippocampus, striatum, and more precisely defined areas within these brain regions where Chrna7 genotype is associated with the level of alpha-bungarotoxin binding. The fact that Chrna7 genotype is linked to individual differences in alpha-bungarotoxin binding, but not alpha 7 RNA levels, suggests that the observed linkage between Chrna7 genotype and alpha-bungarotoxin levels may be due to genetic influences on the post-transcriptional regulation of alpha 7 nicotinic receptor expression. (C) 2009 Elsevier B.V. All rights reserved.