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Loss of pro‐apoptotic BH3‐only Bcl‐2 family member bim does not protect mutant Lurcher mice from neurodegeneration
Author(s) -
Bouillet Philippe,
Robati Mikara,
Adams Jerry M.,
Strasser Andreas
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10805
Subject(s) - neurodegeneration , apoptosis , cerebellum , microbiology and biotechnology , biology , programmed cell death , neuroscience , phenotype , glutamate receptor , receptor , bcl 2 family , gene , genetics , medicine , disease
Lurcher ( lc ) mice have a semi‐dominant mutation in the gene encoding the δ2 glutamate receptor (GRID2). The resulting constitutive activity of this receptor in heterozygous +/ lc ( grid +/ lc ) and homozygous ( grid lc / lc ) mice leads to the death of all cerebellar Purkinje cells and most afferent granule neurons. Some studies have indicated that the death of Purkinje cells occurs by apoptosis, and the secondary loss of granule neurons has been shown to require the pro‐apoptotic Bcl‐2 family member Bax. The BH3‐only protein Bim has been shown to contribute to cytokine withdrawal‐induced apoptosis of sympathetic neurons and to be responsible for the kidney degeneration in mice lacking the pro‐survival protein Bcl‐2. Because Bim is expressed strongly in cerebellar Purkinje cells, we have examined whether it has a role in their death in mutant Lurcher mice. Our studies show that Bim deficiency does not modify the Lurcher phenotype, ruling out an indispensable role for Bim in this neurodegenerative disease. © 2003 Wiley‐Liss, Inc.