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

Huaibin Cai, Xian Lin, Chengsong Xie, Fiona M. Laird, Chen Lai, Hongjin Wen, Hsueh Cheng Chiang, Hoon Shim, Mohamed H. Farah, Ahmet Hoke, Donald L. Price, Philip C. Wong

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Abstract

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.

Original languageEnglish
Pages (from-to)7567-7574
Number of pages8
JournalJournal of Neuroscience
Volume25
Issue number33
DOIs
Publication statusPublished - 2005 Aug 17

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Cai, H., Lin, X., Xie, C., Laird, F. M., Lai, C., Wen, H., Chiang, H. C., Shim, H., Farah, M. H., Hoke, A., Price, D. L., & Wong, P. C. (2005). Loss of ALS2 function is insufficient to trigger motor neuron degeneration in knock-out mice but predisposes neurons to oxidative stress. Journal of Neuroscience, 25(33), 7567-7574. https://doi.org/10.1523/JNEUROSCI.1645-05.2005