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

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, qv^J, qv^2J, qv^3J, qv^4J, qv^lnd and qv^lnd2J, 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 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 origin^4,5,6. 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.