Abstract
Shaker‐type potassium (K+) channels are composed of pore‐forming α subunits associated with cytoplasmic β subunits. Kvβ2 is the predominant Kvβ subunit in the mammalian nervous system, but its functions in vivo are not clear. Kvβ2‐null mice have been previously characterized in our laboratory as having reduced lifespans, cold swim‐induced tremors and occasional seizures, but no apparent defect in Kvα‐subunit trafficking. To test whether strain differences might influence the severity of this phenotype, we analyzed Kvβ2‐null mice in different strain backgrounds: 129/SvEv (129), C57BL/6J (B6) and two mixed B6/129 backgrounds. We found that strain differences significantly affected survival, body weight and thermoregulation in Kvβ2‐null mice. B6 nulls had a more severe phenotype than 129 nulls in these measures; this dramatic difference did not reflect alterations in seizure thresholds but may relate to strain differences we observed in cerebellar Kv1.2 expression. To specifically test whether Kvβ1 is a genetic modifier of the Kvβ2‐null phenotype, we generated Kvβ1.1‐deficient mice by gene targeting and bred them to Kvβ2‐null mice. Kvβ1.1/Kvβ2 double knockouts had significantly increased mortality compared with either single knockout but still maintained surface expression of Kv1.2, indicating that trafficking of this α subunit does not require either Kvβ subunit. Our results suggest that genetic differences between 129/SvEv and C57Bl/6J are key determinants of the severity of defects seen in Kvβ2‐null mice and that Kvβ1.1 is a specific although not strain‐dependent modifier.
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