APOPTOTIC CELL-DEATH IN THE CEREBELLUM OF MUTANT WEAVER AND LURCHER MICE

Apoptosis in the central nervous system of mutant weaver (wv) and lurcher (lc) mice was studied using in situ DNA end-labeling. The number of apoptotic cells in the external granule cell layer of weaver (wv/+) mice at postnatal day 9 was increased six- to eightfold compared to (+/+) littermates. Purkinje cells and Bergmann glia cells were not affected. No labeled cells were found in the substantia nigra. In lurcher (lc/+) mice, labeled nuclei of large cells were found in the Purkinje cell layer, suggesting that Purkinje cells of mutant lurcher mice undergo apoptosis. Apoptotic granule cell nuclei were found in the internal granule cell layer. In contrast to weaver (wv/+) mice, the number of apoptotic cells in the external granule cell layer was not increased. Apoptosis appears to be the common pathway of cell death in the degenerative processes induced by the weaver and the lurcher gene, respectively. These mutant mice offer the opportunity to study the mechanisms that underlie inappropriate apoptotic cell death in vivo.