AN IMMUNOCYTOCHEMICAL STUDY OF A G-PROTEIN-GATED INWARD RECTIFIER K+ CHANNEL (GIRK2) IN THE WEAVER MOUSE MESENCEPHALON

IT has been suggested that a mutation in a G-protein-gated inward rect ifier K+ channel (GIRK2) is responsible for inducing cell death in the cerebellum of homozygous weaver (wv/wv) mutant mice. These mice also display a progressive, massive loss of mesencephalic dopaminergic neur ones. Using an immunocytochemical method, we detected GIRK2-positive c ell bodies and fibres in the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) of control (+/+) mice. Cell counts of both GIRK2- and tyrosine hydroxylase (TH)-positive neurones demonstra ted a marked loss of SNC cell bodies, especially in 12-month-old (12M) wv/wv mice. A considerable proportion of GIRK2-positive cell bodies w ere preserved, however. In addition, no loss of GIRK2-positive neurone s was observed in the VTA of 12M wv/wv mice, despite of a significant reduction in TH-positive cell bodies. These results suggest that expre ssion of the mutated channel is not a sufficient condition to induce c ell death in the ventral mesencephalon of the wv/wv mice.