Girk2 expression in the ventral midbrain, cerebellum, and olfactory bulb and its relationship to the murine mutation weaver

The mouse mutant weaver exhibits developmental deficits and cell death in s everal neuronal classes. weaver is almost certainly a mutation in the potas sium channel, Girk2. In some vulnerable neurons, including those in the mid brain, it is not known whether weaver expression is the primary defect, or whether deficits are secondary to weaver expression elsewhere. In wild-type mice, our results point to subsets of dopamine-containing cells of the mid brain as primary targets of weaver. In the midbrain, all Girk2-positive cel ls examined in A9 (substantia nigra), A10, and A8 (retrorubral nucleus) are tyrosine hydroxylase-positive. The expression of Girk2 varies among and wi thin these regions. Girk2-positive cells are most numerous in the substanti a nigra, pars compacta, a region badly affected in homozygous weavers; in t his region, Girk2 expression is found in cell somata and dendrites. In addi tion, in homozygous weavers, the remaining neuronal processes in A9 (as wel l as A8) are stunted. Within A10, a region largely spared in weaver homozyg otes, Girk2 expression is undetectable in the most medially placed nuclei a nd is present in the nuclei that border A9. In the cerebellum, Girk2 immuno reactivity was also found in somata and dendrites of populations vulnerable to weaver, including the deep cerebellar nuclei. In a region not previousl y known to be affected, the olfactory bulb, Girk2 protein is detectable onl y in processes. The expression of mutated Girk2 has consequences for the ol factory bulb where ectopic cells are present in the external plexiform laye r of the homozygous weaver. Our results emphasize that the Girk2 mutation m ay act to alter the development and maintenance of cell processes and that defects may be present in all Girk2-containing regions in weaver mutants. ( C) 1998 Academic Press.