Developmental expression of the GIRK family of inward rectifying XXXX channels: implications for abnormalities in the weaver mutant @entity19 .

@entity19 @entity535 @entity32592 @entity51617 @entity972 @entity51616
G-protein-gated inward rectifying @entity972 channels (GIRKs) are a newly identified gene family. These gene products are thought to form functional channels through the assembly of heteromeric subunits. Recently, it has been demonstrated that a point mutation in the @entity32592 gene, one of the GIRK family members, is the cause of the neurological and reproductive defects observed in the weaver (wv) mutant @entity19 . The mechanism(s) by which a single @entity535 substitution in @entity32592 protein leads to the severe phenotypes in the wv / wv @entity19 is not fully understood. However, it implicates the importance of GIRK channels in neuronal development. To characterize the mRNA expression patterns of @entity51616 -3 during @entity19 brain development we have used in situ hybridization analyses. We found that the expression of all three genes showed developmental regulation. In most areas that showed expression, the levels of @entity51616 -3 transcripts reached their peak at around postnatal day 10 (P10). In general, @entity51616 showed the least fluctuation in its levels of expression during development, while dynamic changes were found with the levels of @entity32592 and @entity51617 transcripts. @entity51617 becomes the predominant inward rectifying K+-channel in the brain at later postnatal ages. In the CNS regions affected in the wv / wv @entity19 , @entity32592 is the predominant inward rectifying channel that is expressed. This suggests that the presence of the other subtypes are able to compensate for the mutated @entity32592 channel in weaver neurons that survive.
