Proprioceptive sensory neuropathy in mice with a mutation in the cytoplasmic dynein heavy chain 1 gene

Xiang Jun Chen, Eleni N. Levedakou, Kathleen J. Millen, Robert L. Wollmann, Betty Soliven, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Mice heterozygous for the radiation-induced Sprawling (Swl) mutation display an early-onset sensory neuropathy with muscle spindle deficiency. The lack of an H reflex despite normal motor nerve function in the hindlimbs of these mutants strongly suggests defective proprioception. Immunohistochemical analyses reveal that proprioceptive sensory neurons are severely compromised in the lumbar dorsal root ganglia of newborn Swl/+ mice, whereas motor neuron numbers remain unaltered even in aged animals. We have used positional cloning to identify a nine base-pair deletion in the cytoplasmic dynein heavy chain 1 gene (Dync1h1) in this mutant. Furthermore, we demonstrate that Loa/+ mice, which have previously been shown to carry a missense point mutation in Dync1h1 that results in late-onset motor neuron loss, also present with a severe, early-onset proprioceptive sensory neuropathy. Interestingly, in contrast to the Loa mutation, the Swl mutation does not delay disease progression in a motor neuron disease mouse model overexpressing a human mutant superoxide dismutase (SOD1G93A) transgene. Together,weprovide in vivo evidence that distinct mutations in cytoplasmic dynein can either result in a pure sensory neuropathy or in a sensory neuropathy with motor neuron involvement.

Original languageEnglish (US)
Pages (from-to)14515-14524
Number of pages10
JournalJournal of Neuroscience
Issue number52
StatePublished - Dec 26 2007


  • Charcot-Marie-Tooth disease
  • Dorsal root ganglia
  • Dynein
  • Gene deletion
  • Mouse mutant
  • Sensory neuron degeneration

ASJC Scopus subject areas

  • Neuroscience(all)

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