title: Premature aging-related peripheral neuropathy in a mouse model of progeria.
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.
authors: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, PA 15213-1863, USA. jrgoss@pitt.edu
authors: James R
authors: JR
authors: Goss
authors: Donna Beer
authors: DB
authors: Stolz
authors: Andria Rasile
authors: AR
authors: Robinson
authors: Mingdi
authors: M
authors: Zhang
authors: Norma
authors: N
authors: Arbujas
authors: Paul D
authors: PD
authors: Robbins
authors: Joseph C
authors: JC
authors: Glorioso
authors: Laura J
authors: LJ
authors: Niedernhofer
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