Quivering (qv) mutants of the spectrin beta, non-erythrocytic 4 (Sptbn4) are characterized by progressive ataxia with hind limb paralysis, deafness and tremor. These quivering 4 Jackson mice carry a spontaneous mutation at the Sptbn4 locus characterized by an aberrant TREK-1 potassium channel.Read More +
Beta-spectrin 4 is critical for the local organization of protein complexes throughout the nervous system. It targets ion channels and adapter proteins to axon initial segments and nodes of Ranvier in neurons, and beta-spectrin 4 dysfunction underlies ataxia and early death in mice. Beta-spectrin 4 is also co-localized with TREK-1 at the myocyte intercalated disc, associates with TREK-1 in the heart, and is required for TREK-1 membrane targeting. Mice expressing Sptbn4qv-4J lack TREK-1 binding and display aberrant TREK-1 membrane localization, decreased TREK-1 activity, delayed action potential repolarization, and arrhythmia without apparent defects in localization/function of other cardiac potassium channel subunits.
The Sptbn4qv-4J mutation is a C to T transition point mutation at residue 4234, which introduces a premature stop codon at a position corresponding to amino acid 1358 in the encoded protein.
|Allele Name||quivering 4 Jackson|
|Gene Symbol and Name||Sptbn4, spectrin beta, non-erythrocytic 4|
|Strain of Origin||C57BL/6ByJ x DBA/2J|
|Molecular Note||The mutation is a C-to-T transition point mutation at coding nucleotide 4234 (transcript XM_006540436), which introduces a premature stop codon at a position corresponding to glutamine 1412 in the encoded protein (p.Q1412*).|