Developmental expression of the GIRK family of inward rectifying potassium channels: implications for abnormalities in the weaver mutant mouse.

G-protein-gated inward rectifying potassium 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 GIRK2 gene, one of the GIRK family members, is the cause of the neurological and reproductive defects observed in the weaver (wv) mutant mouse. The mechanism(s) by which a single amino acid substitution in GIRK2 protein leads to the severe phenotypes in the wv / wv mouse is not fully understood. However, it implicates the importance of GIRK channels in neuronal development. To characterize the mRNA expression patterns of GIRK1-3 during mouse 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 GIRK1-3 transcripts reached their peak at around postnatal day 10 (P10). In general, GIRK1 showed the least fluctuation in its levels of expression during development, while dynamic changes were found with the levels of GIRK2 and GIRK3 transcripts. GIRK3 becomes the predominant inward rectifying K+-channel in the brain at later postnatal ages. In the CNS regions affected in the wv / wv mouse, GIRK2 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 GIRK2 channel in weaver neurons that survive.