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Biochem Biophys Res Commun. 2009 May 29;383(2):258-62. doi: 10.1016/j.bbrc.2009.04.009. Epub 2009 Apr 7.

Impaired regenerative response of primary sensory neurons in ZPK/DLK gene-trap mice.

Author information

1
Department of Neurology, School of Medicine, University of California, Davis, 601A Shriners Hospitals for Children Northern California, Sacramento, CA 95817-2215, USA.

Abstract

Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in regenerative responses of mammalian DRG neurons to axonal injury through activation of c-JUN.

PMID:
19358824
DOI:
10.1016/j.bbrc.2009.04.009
[Indexed for MEDLINE]

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