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 new ly identified gene family. These gene products are thought to form fun ctional channels through the assembly of heteromeric subunits. Recentl y, it has been demonstrated that a point mutation in the GIRK2 gene, o ne of the GIRK family members, is the cause of the neurological and re productive defects observed in the wearier (wv) mutant mouse. The mech anism(s) by which a single amino acid substitution in GIRK2 protein le ads to the severe phenotypes in the wu/wu mouse is not fully understoo d. However, it implicates the importance of GIRK channels in neuronal development. To characterize the mRNA expression patterns of GIRK 1-3 during mouse brain development we have used in sim hybridization analy ses. We found that the expression of all three genes showed developmen tal regulation. In most areas that showed expression, the levels of GI RK 1-3 transcripts reached their peak at around postnatal day 10 (P10) . In, general, GIRK 1 showed the least fluctuation in its levels of ex pression 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 wu/wu mouse, GIRK2 is the predominant inward rectifying channel that is expressed. This suggests that the pr esence of the other subtypes art, able to compensate for the mutated G IRK2 channel in wearier neurons that survive. (C) 1997 Elsevier Scienc e B.V.