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 journalArticlepeer-review

34 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 2011
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health grants ES016114 and 03S to L.J.N. and CA076541 to D.B.S., the Ellison Medical Foundation (AG-NS-0303-05; L.J.N.), and Pilot Projects from the University of Pittsburgh Claude B. Pepper Center (P30AG024827; PI: Studenski) and a Pilot the Pittsburgh Center for Kidney Research (P30DK079307; PI Kleyman). P.D.R is supported by National Institutes of Health grants NS058451, AG024827, AG033907 and AR051456. J.C.G. is supported by National Institutes of Health grants DK04493 and CA119298.


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


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