Sequence of the voltage-gated sodium channel beta1-subunit in wild-type and in quivering mice.

ABSTRACT

SCN1B, the human gene encoding the beta1-subunit of the voltage-gated sodium channel has previously been cloned and mapped to Chr 19q13.1. The sequence of the homologous mouse gene, Scn1b, has now been determined from cDNA. The mouse gene is highly conserved, encoding a predicted protein with 99%, 98% and 96% amino acid identity to the rat, rabbit, and human homologs, respectively. DNA sequence conservation is also striking in the 3' untranslated region which shows 67% and 98% to human and rat, respectively. Unlike the human and rat homologs, high expression of mRNA from the mouse gene is confined to adult skeletal muscle and brain, and is not observed in heart. As Scnlb maps to Chr 7, in close genetic proximity to the quivering gene (qv), the coding region of Scnlb was also cloned from a qvJ/qvJ homozygous mouse and assessed as a candidate for the site of this genetic defect. Comparison of qv and wild-type cDNAs showed no changes in the predicted amino acid sequence that could cause the qv phenotype. However, three silent polymorphisms in the DNA coding region indicate that Scn1b is close to qv, and is within a region of genetic identity with DBA/2J, the inbred background on which the qvJ allele arose.