Neurodegeneration in Lurcher mice occurs via multiple cell death pathways

Citation
Ml. Doughty et al., Neurodegeneration in Lurcher mice occurs via multiple cell death pathways, J NEUROSC, 20(10), 2000, pp. 3687-3694
Citations number
38
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
02706474 → ACNP
Volume
20
Issue
10
Year of publication
2000
Pages
3687 - 3694
Database
ISI
SICI code
0270-6474(20000515)20:10<3687:NILMOV>2.0.ZU;2-6
Abstract
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.