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Cell. 1993 Apr 9;73(1):35-46.

Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis.

Author information

1
Centre for Research in Neurosciences McGill University, Canada.

Abstract

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.

PMID:
8462101
DOI:
10.1016/0092-8674(93)90158-m
[Indexed for MEDLINE]

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