Bcl-2 overexpression does not protect neurons from mutant neurofilament-mediated motor neuron degeneration.
Transgenic mice with a point mutation in the light neurofilament gene develop amyotrophic lateral sclerosis-like motor neuron disease characterized by selective spinal motor neuron loss, neurofilamentous accumulations, and severe muscle atrophy. To test whether the large motor neurons at risk in this disease could be protected from mutant neurofilament-mediated killing, these mice were bred to mice overexpressing the human Bcl-2 proto-oncogene. Elevated levels of Bcl-2 increased the numbers of motor and sensory axons surviving after the developmental period of naturally occurring cell death but did not greatly reduce the number of degenerating axons or protect the large motor neurons from mutant neurofilament-mediated death.
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, California 92093, USA.
M K
MK
Houseweart
D W
DW
Cleveland
D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008136:Longevity / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000502:physiology; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009154:Mutation / Q000502:physiology*; D009410:Nerve Degeneration / Q000503:physiopathology*; D016900:Neurofilament Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors
C000715470:MAS1 protein, human; D016900:Neurofilament Proteins; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; C044882:neurofilament protein L