Unique cerebellar phenotype combining granule and Purkinje cell loss: Morphological evidence forweaver*pcd double mutant mice

Summary Weaver (wv/wv) mutant mice lose most granule cells of the cerebellum during the first 2 weeks of postnatal life; ‘Purkinje cell degeneration’ (pcd/pcd) mutants lose virtually all Purkinje cells between postnatal days 17 and 45. Both these neurological mutations are autosomal recessive. We designed a breeding protocol that, in theory, should result in the production of mice with a doubly mutant,wv/wv*pcd/pcd, genotype. Some of the offspring of such crosses had a novel cerebellar phenotype in which both granule and Purkinje cells underwent degeneration, leading to a highly atrophic cortex. This phenotype is what would be expected inwv/wv*pcd/pcd double mutants, and the proportion of such progeny obtained fits with genetic expectations. We propose that (1)wv/wv*pcd/pcd double mutant mice are viable, and (2) the anatomical phenotype of such mice is a combined expression of the component phenotypes.