| First Author | Burgess DL | Year | 1997 |
| Journal | Cell | Volume | 88 |
| Issue | 3 | Pages | 385-92 |
| PubMed ID | 9039265 | Mgi Jnum | J:38214 |
| Mgi Id | MGI:85602 | Doi | 10.1016/s0092-8674(00)81877-2 |
| Citation | Burgess DL, et al. (1997) Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell 88(3):385-92 |
| abstractText | Ca2+ channel beta subunits regulate voltage-dependent calcium currents through direct interaction with alpha(1) subunits. The beta- and alpha(1)-binding motifs are conserved, and all beta subunits can stimulate current amplitude, voltage dependence, and kinetics when coexpressed with various alpha(1) subunits. We used a positional candidate approach to determine that the ataxia and seizures in the lethargic (lh) mouse arise from mutation of the beta-subunit gene Cchb4 on mouse chromosome 2. A four-nucleotide insertion into a splice donor site results in exon skipping, translational frameshift, and protein truncation with loss of the alpha(1)-binding site. The lethargic phenotype is the first example of a mammalian neurological disease caused by an inherited defect in a non-pore-forming subunit of a voltage-gated ion channel. |
