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Mech Ageing Dev. 2011 Aug;132(8-9):437-42. doi: 10.1016/j.mad.2011.04.010. Epub 2011 May 11.

Premature aging-related peripheral neuropathy in a mouse model of progeria.

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1
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, PA 15213-1863, USA. jrgoss@pitt.edu

Abstract

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies.

PMID:
21596054
PMCID:
PMC3179831
DOI:
10.1016/j.mad.2011.04.010
[Indexed for MEDLINE]
Free PMC Article

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