PMID:10884316

Citation	Beaulieu, JM, Jacomy, H and Julien, JP (2000) Formation of intermediate filament protein aggregates with disparate effects in two transgenic mouse models lacking the neurofilament light subunit. J. Neurosci. 20:5321-8
Abstract	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.
Links	PubMed
Keywords	Animals; Axons/metabolism; Axons/pathology; Blotting, Western; Chymotrypsinogen/chemistry; Cytoplasm/metabolism; Disease Models, Animal; Gene Targeting; Humans; Inclusion Bodies/chemistry; Inclusion Bodies/genetics; Inclusion Bodies/metabolism; Inclusion Bodies/pathology; Intermediate Filament Proteins/biosynthesis; Membrane Glycoproteins; Mice; Mice, Transgenic; Motor Neuron Disease/genetics; Motor Neuron Disease/metabolism; Motor Neuron Disease/pathology; Motor Neurons/metabolism; Motor Neurons/pathology; Nerve Tissue Proteins/biosynthesis; Neurofilament Proteins/biosynthesis; Neurofilament Proteins/chemistry; Neurofilament Proteins/deficiency; Neurofilament Proteins/genetics; Octoxynol/chemistry; Protein Structure, Tertiary
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.