| First Author | Beaulieu JM | Year | 2000 |
| Journal | J Neurosci | Volume | 20 |
| Issue | 14 | Pages | 5321-8 |
| PubMed ID | 10884316 | Mgi Jnum | J:63482 |
| Mgi Id | MGI:1861055 | Doi | 10.1523/JNEUROSCI.20-14-05321.2000 |
| Citation | Beaulieu JM, et al. (2000) Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit. J Neurosci 20(14):5321-8 |
| abstractText | Protein aggregates containing intermediate filaments (IFs) are a hallmark of degenerating spinal motor neurons in amyotrophic lateral sclerosis (ALS). Recently, we reported that a deficiency in neurofilament light subunit (NF-L), a phenomenon associated with ALS, promoted the formation of IF inclusions with ensuing motor neuron death in transgenic mice overproducing peripherin, a type III IF protein detected in axonal inclusions of ALS patients. To further assess the role of NF-L in the formation of abnormal IF inclusions, we generated transgenic mice overexpressing human neurofilament heavy subunits (hNF-H) in a context of targeted disruption of the NF-L gene (hH;L-/- mice). The hH;L-/- mice exhibited motor dysfunction, and they developed nonfilamentous protein aggregates containing NF-H and peripherin proteins in the perikarya of spinal motor neurons. However, the perikaryal protein aggregates in the hH;L-/- mice did not provoke motor neuron death, unlike toxic IF inclusions induced by peripherin overexpression in NF-L null mice (Per;L-/- mice). Our results indicate that different types of IF protein aggregates with distinct properties may occur in a context of NF-L deficiency and that an axonal localization of such aggregates may be an important factor of toxicity. |
