Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease

Luc Dupuis, Anissa Fergani, Kerstin E. Braunstein, Judith Eschbach, Nathalie Holl, Frédérique Rene, Jose Luis Gonzalez De Aguilar, Björn Zoerner, Birgit Schwalenstocker, Albert C. Ludolph, Jean Philippe Loeffler

Research output: Contribution to journalArticle

Abstract

In neurons, cytoplasmic dynein functions as a molecular motor responsible for retrograde axonal transport. An impairment of axonal transport is thought to play a key role in the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis, the most frequent motor neuron disease in the elderly. In this regard, previous studies described two heterozygous mouse strains bearing missense point mutations in the dynein heavy chain 1 gene that were reported to display late-onset progressive motor neuron degeneration. Here we show, however, that one of these mutant strains, the so-called Cra mice does not suffer from motor neuron loss, even in aged animals. Consistently, we did not observe electrophysiological or biochemical signs of muscle denervation, indicative of motor neuron disease. The «hindlimb clasping» phenotype of Cra mice could rather be due to the prominent degeneration of sensory neurons associated with a loss of muscle spindles. Altogether, these findings show that dynein heavy chain mutation triggers sensory neuropathy rather than motor neuron disease.

Original languageEnglish (US)
Pages (from-to)146-152
Number of pages7
JournalExperimental Neurology
Volume215
Issue number1
DOIs
StatePublished - Jan 2009
Externally publishedYes

Fingerprint

Dyneins
Motor Neuron Disease
Axonal Transport
Motor Neurons
Mutation
Cytoplasmic Dyneins
Muscle Denervation
Genes
Muscle Spindles
Nerve Degeneration
Amyotrophic Lateral Sclerosis
Sensory Receptor Cells
Missense Mutation
Hindlimb
Point Mutation
Neurodegenerative Diseases
Phenotype
Neurons

Keywords

  • Amyotrophic lateral sclerosis
  • Axonal transport
  • Dynein
  • Motor neuron

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Neurology

Cite this

Dupuis, L., Fergani, A., Braunstein, K. E., Eschbach, J., Holl, N., Rene, F., ... Loeffler, J. P. (2009). Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease. Experimental Neurology, 215(1), 146-152. https://doi.org/10.1016/j.expneurol.2008.09.019

Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease. / Dupuis, Luc; Fergani, Anissa; Braunstein, Kerstin E.; Eschbach, Judith; Holl, Nathalie; Rene, Frédérique; Gonzalez De Aguilar, Jose Luis; Zoerner, Björn; Schwalenstocker, Birgit; Ludolph, Albert C.; Loeffler, Jean Philippe.

In: Experimental Neurology, Vol. 215, No. 1, 01.2009, p. 146-152.

Research output: Contribution to journalArticle

Dupuis, L, Fergani, A, Braunstein, KE, Eschbach, J, Holl, N, Rene, F, Gonzalez De Aguilar, JL, Zoerner, B, Schwalenstocker, B, Ludolph, AC & Loeffler, JP 2009, 'Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease', Experimental Neurology, vol. 215, no. 1, pp. 146-152. https://doi.org/10.1016/j.expneurol.2008.09.019
Dupuis, Luc ; Fergani, Anissa ; Braunstein, Kerstin E. ; Eschbach, Judith ; Holl, Nathalie ; Rene, Frédérique ; Gonzalez De Aguilar, Jose Luis ; Zoerner, Björn ; Schwalenstocker, Birgit ; Ludolph, Albert C. ; Loeffler, Jean Philippe. / Mice with a mutation in the dynein heavy chain 1 gene display sensory neuropathy but lack motor neuron disease. In: Experimental Neurology. 2009 ; Vol. 215, No. 1. pp. 146-152.
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