| First Author | Plummer J | Year | 1995 |
| Journal | Mol Cell Neurosci | Volume | 6 |
| Issue | 6 | Pages | 532-43 |
| PubMed ID | 8742270 | Mgi Jnum | J:31812 |
| Mgi Id | MGI:79306 | Doi | 10.1006/mcne.1995.0005 |
| Citation | Plummer J, et al. (1995) Accelerated and widespread neuronal loss occurs in motor neuron degeneration (mnd) mice expressing a neurofilament-disrupting transgene. Mol Cell Neurosci 6(6):532-43 |
| abstractText | To examine the effects of multiple stressors on the onset and specificity of a neurodegenerative disease, we derived mnd/mnd mice expressing a neurofilament-H/lacZ transgene. The mnd mutation causes adult-onset motor dysfunction, and produces abnormal ubiquitous accumulation of autofluorescent lipopigment, with retinal degeneration and late-onset motor neuron degeneration. The neurofilament H-beta-galactosidase fusion protein causes endogenous neurofilament subunits to precipitate in perikarya, but shows neither significant neuronal degeneration nor behavioral changes until advanced age. In mnd/mnd-transgenic animals, neurological symptoms, lipopigment accumulation, and motor neuron loss were substantially accelerated. Newly vulnerable populations of neurons also degenerated, including cerebellar Purkinje cells and dorsal roots. This study exemplifies a synergistic interaction between a neuron-specific and a ubiquitous defect, leading to significant neurological consequences. It further indicates that cytoskeletal abnormalities similar to those observed in late-onset human neurodegenerative disorders can interact with other cellular defects and contribute to pathogenesis. |
