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

James R. Goss, Donna Beer Stolz, Andria Rasile Robinson, Mingdi Zhang, Norma Arbujas, Paul D. Robbins, Joseph C. Glorioso, Laura J. Niedernhofer

Research output: Contribution to journalArticle

27 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)437-442
Number of pages6
JournalMechanisms of Ageing and Development
Issue number8-9
StatePublished - Aug 1 2011
Externally publishedYes


  • DNA repair
  • Nerve conduction
  • Nerve morphology
  • Neurodegeneration
  • Progeria
  • Xeroderma pigmentosum

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