title: Loss of pro-apoptotic BH3-only Bcl-2 family member Bim does not protect mutant Lurcher mice from neurodegeneration.
abstract: Lurcher (lc) mice have a semi-dominant mutation in the gene encoding the delta2 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.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia. bouillet@wehi.edu.au
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.forename: Mikara
authors.initials: M
authors.lastname: Robati
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Adams
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology*; D008565:Membrane Proteins; D051379:Mice; D008818:Mice, Neurologic Mutants; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics* / Q000473:pathology; D011518:Proto-Oncogene Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins