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Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress.

Amyotrophic lateral sclerosis (ALS), the most common motor neuron disease, is caused by a selective loss of motor neurons in the CNS. Mutations in the ALS2 gene have been linked to one form of autosomal recessive juvenile onset ALS (ALS2). To investigate the pathogenic mechanisms of ALS2, we generated ALS2 knock-out (ALS2(-/-)) mice. Although ALS2(-/-) mice lacked obvious developmental abnormalities, they exhibited age-dependent deficits in motor coordination and motor learning. Moreover, ALS2(-/-) mice showed a higher anxiety response in the open-field and elevated plus-maze tasks. Although they failed to recapitulate clinical or neuropathological phenotypes consistent with motor neuron disease by 20 months of age, ALS2(-/-) mice or primary cultured neurons derived from these mice were more susceptible to oxidative stress compared with wild-type controls. These observations suggest that loss of ALS2 function is insufficient to cause major motor deficits or motor neuron degeneration in a mouse model but predisposes neurons to oxidative stress.

Pubmed ID: 16107644

Authors

  • Cai H
  • Lin X
  • Xie C
  • Laird FM
  • Lai C
  • Wen H
  • Chiang HC
  • Shim H
  • Farah MH
  • Hoke A
  • Price DL
  • Wong PC

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

August 17, 2005

Associated Grants

  • Agency: NINDS NIH HHS, Id: R01 NS40014
  • Agency: Intramural NIH HHS, Id: Z01 AG000959-04
  • Agency: Intramural NIH HHS, Id: Z99 AG999999

Mesh Terms

  • Amyotrophic Lateral Sclerosis
  • Animals
  • Anxiety
  • Cells, Cultured
  • Female
  • Guanine Nucleotide Exchange Factors
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Neurons
  • Motor Skills
  • Nerve Degeneration
  • Neurons
  • Oxidative Stress