Abstract
The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor1. Six additional spontaneous alleles, qvJ, qv2J, qv3J, qv4J, qvlnd and qvlnd2J, have been identified2,3. Ear twitch responses (Preyer's reflex) to sound are absent in homozygous qv/qv mice, although cochlear morphology seems normal and cochlear potentials recorded at the round window are no different from those of control mice4. However, responses from brainstem auditory nuclei show abnormal transmission of auditory information, indicating that, in contrast to the many known mutations causing deafness originating in the cochlea, deafness in qv is central in origin4,5,6. Here we report that quivering mice carry loss-of-function mutations in the mouse β-spectrin 4 gene (Spnb4) that cause alterations in ion channel localization in myelinated nerves; this provides a rationale for the auditory and motor neuropathies of these mice.
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Acknowledgements
This work was supported by National Institutes of Health DC02739 and DC04661 (B.L T.), a Medical Research Council Fellowship (N.J.P.), National Institutes of Health Training Grant DC00018 (B.P.K.), National Institute on Deafness and Other Communication Disorders Z01DC00056-01 (K.N.T.) and a Howard Hughes Medical Institute Pilot Grant (S.G.K.). We thank L. Robinson for providing all the mice, C. Kozak for monochromosomal cell lines and S.D.M. Brown of the Medical Research Council Mouse Genome Centre for supporting the completion of this work.
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Parkinson, N., Olsson, C., Hallows, J. et al. Mutant β-spectrin 4 causes auditory and motor neuropathies in quivering mice. Nat Genet 29, 61–65 (2001). https://doi.org/10.1038/ng710
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DOI: https://doi.org/10.1038/ng710
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