| First Author | Schilling G | Year | 1999 |
| Journal | Neuron | Volume | 24 |
| Issue | 1 | Pages | 275-86 |
| PubMed ID | 10677044 | Mgi Jnum | J:70362 |
| Mgi Id | MGI:2137111 | Doi | 10.1016/s0896-6273(00)80839-9 |
| Citation | Schilling G, et al. (1999) Nuclear accumulation of truncated atrophin-1 fragments in a transgenic mouse model of DRPLA. Neuron 24(1):275-86 |
| abstractText | Dentatorubral and pallidoluysian atrophy (DRPLA) is a member of a family of progressive neurodegenerative diseases caused by polyglutamine repeat expansion. Transgenic mice expressing full-length human atrophin-1 with 65 consecutive glutamines exhibit ataxia, tremors, abnormal movements, seizures, and premature death. These mice accumulate atrophin-1 immunoreactivity and inclusion bodies in the nuclei of multiple populations of neurons. Subcellular fractionation revealed 120 kDa nuclear fragments of mutant atrophin-1, whose abundance increased with age and phenotypic severity. Brains of DRPLA patients contained apparently identical 120 kDa nuclear fragments. By contrast, mice overexpressing atrophin-1 with 26 glutamines were phenotypically normal and did not accumulate the 120 kDa fragments. We conclude that the evolution of neuropathology in DRPLA involves proteolytic processing of mutant atrophin-1 and nuclear accumulation of truncated fragments. |
