| First Author | Côté F | Year | 1993 |
| Journal | Cell | Volume | 73 |
| Issue | 1 | Pages | 35-46 |
| PubMed ID | 8462101 | Mgi Jnum | J:69180 |
| Mgi Id | MGI:1934183 | Doi | 10.1016/0092-8674(93)90158-m |
| Citation | Cote F, et al. (1993) Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell 73(1):35-46 |
| abstractText | We generated four transgenic mice with a 34 kb genomic fragment including the complete human neurofilament heavy (NF-H) gene. This human NF-H fragment contained all regulatory elements for tissue-specific expression, and in two transgenic lines, human NF-H proteins were produced at levels up to 2-fold the levels of endogenous mouse NF-H protein. By 3-4 months of age, these NF-H transgenics progressively develop neurological defects and abnormal neurofilamentous swellings that are highly reminiscent of those found in amyotrophic lateral sclerosis (ALS). We propose that a modest up-regulation of NF-H cross-linkers can result in an impairment of neurofilament transport, causing neuronal swellings with ensuing axonopathy and muscle atrophy, a mechanism of pathogenesis pertinent to the possible etiology of ALS. |
