Abnormal neurofilament transport caused by targeted disruption of neuronal kinesin heavy chain KIF5A

Chun Hong Xia, Elizabeth A. Roberts, Lu Shiun Her, Xinran Liu, David S. Williams, Don W. Cleveland, Lawrence S.B. Goldstein

研究成果: Article同行評審

246 引文 斯高帕斯(Scopus)

摘要

To test the hypothesis that fast anterograde molecular motor proteins power the slow axonal transport of neurofilaments (NFs), we used homologous recombination to generate mice lacking the neuronal-specific conventional kinesin heavy chain, KIF5A. Because null KIF5A mutants die immediately after birth, a synapsin-promoted Cre-recombinase transgene was used to direct inactivation of KIF5A in neurons postnatally. Three fourths of such mutant mice exhibited seizures and death at around 3 wk of age; the remaining animals survived to 3 mo or longer. In young mutant animals, fast axonal transport appeared to be intact, but NF-H, as well as NF-M and NF-L, accumulated in the cell bodies of peripheral sensory neurons accompanied by a reduction in sensory axon caliber. Older animals also developed age-dependent sensory neuron degeneration, an accumulation of NF subunits in cell bodies and a reduction in axons, loss of large caliber axons, and hind limb paralysis. These data support the hypothesis that a conventional kinesin plays a role in the microtubule-dependent slow axonal transport of at least one cargo, the NF proteins.

原文English
頁(從 - 到)55-66
頁數12
期刊Journal of Cell Biology
161
發行號1
DOIs
出版狀態Published - 2003 四月 14

All Science Journal Classification (ASJC) codes

  • Cell Biology

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