Cell death during development of testis and cerebellum in the mutant mouse weaver

The murine mutation weaver confers early death during development on cells in testes, cerebellum, and midbrain. The results reported here support the hypothesis that the action of weaver is intrinsic to testes and independent of Sertoli cells: germ cells are the only testicular cell type seen to die in weaver homozygotes, while Sertoli cell-dependent development of the blood testis barrier is normal. This report includes characterization of patterns of germ cell death and cerebellar granule cell death in homozygous weavers with respect to that seen during normal development by in situ end-labeling of DNA and high-magnification light microscopy. Comparison of the spatial distribution of dying cells in the weaver's cerebellum with that of dividing cells revealed disarray in the external germinal zone. The results show that cells vulnerable to weaver die by apoptotic and nonapoptotic mechanisms and indicate that weaver-induced cell death is not the consequence of extended naturally occurring developmental cell death, although their timing overlaps. Thus, although the death of cells in each region is likely to be caused by the same mutation, a base pair substitution in the G protein-coupled inwardly rectifying potassium channel 2 gene, the cell death program activated differs depending on cell type.