Lurcher (Lc) is a gain-of-function mutation in the delta 2 glutamate recept
or (GRID2) that results in the cell-autonomous death of cerebellar Purkinje
cells in heterozygous lurcher (+/Lc) mice. This in turn triggers the massi
ve loss of afferent granule cells during the first few postnatal weeks. Evi
dence suggests that the death of Purkinje cells as a direct consequence of
GRID2 Lc activation and the secondary death of granule cells because of tar
get deprivation occur by apoptosis. We have used mice carrying null mutatio
ns of both the Bax and p53 genes to examine the roles of these genes in cel
l loss in lurcher animals. The absence of Bax delayed Purkinje cell death i
n response to the GRID2 Lc mutation and permanently rescued the secondary d
eath of granule cells. In contrast, the p53 deletion had no effect on eithe
r cell death pathway. Our results demonstrate that target deprivation induc
es a Bax-dependent, p53-independent cell death response in cerebellar granu
le cells in vivo. In contrast, Bax plays a minor role in GRID2(Lc)-mediated
Purkinje cell death.