Mutant β-spectrin 4 causes auditory and motor neuropathies in quivering mice

被引:101
作者
Parkinson, NJ
Olsson, CL
Hallows, JL
McKee-Johnson, J
Keogh, BP
Noben-Trauth, K
Kujawa, SG
Tempel, BL [1 ]
机构
[1] Univ Washington, Sch Med, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA
[3] Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA
[4] Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, NIH, Rockville, MD USA
关键词
D O I
10.1038/ng710
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor(1). Six additional spontaneous alleles, qv(J), qv(2J), qv(3J), qv(4J) qv(ind) and qv(Ind2J), have been identified(2,3). 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 mice(4). 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 origin(4-6). Here we report that quivering mice carry loss-of-function mutations in the mouse beta -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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页码:61 / 65
页数:5
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