Cell death, Bcl-2, Bax, and the cerebellum.
Bax and Bcl-2 are prototypical members of a large family of Bcl-2-like proteins that play a key role in regulating programmed cell death in many cell types. The purpose of this review is to summarize recent findings about the role of Bcl-2 and Bax in regulating programmed cell death in the cerebellum during normal development and in a mouse model of cell autonomous and target-related cell death, the Lurcher mutant. Both Bcl-2 and Bax are expressed in the developing cerebellum and recent studies of Bcl-2 transgenic mice and Bcl-2 or Bax knock-out mutants have shown that both proteins are likely to play a role in regulating cell death among Purkinje cells, granule cells and olivary neurons. However, the evidence suggests that there are diverse cell death pathways in cerebellar neurons that vary depending on the cell type and cell death stimulus. For example, the number of Purkinje cells is increased by over 30% in one line of Bcl-2 overexpressing transgenics and in Bax knock-out mutants, suggesting that both proteins may be involved in naturally occurring Purkinje cell death. However, overexpression of Bcl-2 or deletion of Bax expression in heterozygous Lurcher mutants delays but does not prevent the cell autonomous death of Lurcher Purkinje cells. The deletion of Bax expression from granule cells does not affect their number in adult Bax knock-out mutants, suggesting that Bax is not involved in naturally occurring granule cell death. However, Bax does appear to be involved in granule cell target-related cell death since substantially more granule cells survive in Bax -/-: Lurcher double mutants than in control Lurcher mutants. In contrast, deletion of Bax expression in Lurcher mutants does not prevent olivary neuron target-related cell death in the Lurcher mutant while overexpression of Bcl-2 in olivary neurons rescues them from both target-related and naturally occurring cell death.
Vogel
Michael W
MW
Maryland Psychiatric Research Center, Baltimore, Maryland 21228, USA. mvogel@mprc.umaryland.edu
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002452:Cell Count; D002478:Cells, Cultured; D002531:Cerebellum / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology; D051381:Rats; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; C494828:Bax protein, rat; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein