Chrna7 genotype is linked with alpha7 nicotinic receptor expression but not alpha7 RNA levels.
Studies using the radio-labeled nicotinic receptor antagonist [(125)I]-alpha-bungarotoxin, which binds to alpha7 subunit containing nicotinic receptors, have demonstrated that mouse strains vary considerably in the number of alpha7-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 alpha7 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 alpha7 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 alpha7 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 alpha7 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 alpha7 nicotinic receptor expression.
Brooks
Nathanial P
NP
Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80303, USA.
Mexal
Sharon
S
Stitzel
Jerry A
JA
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D002038:Bungarotoxins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006624:Hippocampus / Q000378:metabolism; D007457:Iodine Radioisotopes; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D012313:RNA / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000096:biosynthesis* / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579166:Chrna7 protein, mouse; D007457:Iodine Radioisotopes; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D012313:RNA