| First Author | Goss JR | Year | 2011 |
| Journal | Mech Ageing Dev | Volume | 132 |
| Issue | 8-9 | Pages | 437-42 |
| PubMed ID | 21596054 | Mgi Jnum | J:335409 |
| Mgi Id | MGI:7435455 | Doi | 10.1016/j.mad.2011.04.010 |
| Citation | Goss JR, et al. (2011) Premature aging-related peripheral neuropathy in a mouse model of progeria. Mech Ageing Dev 132(8-9):437-42 |
| abstractText | 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(-/Delta) 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(-/Delta) 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. |
