Key result
Targeted deletion of Kcne3 impaired skeletal muscle function, evidenced by abnormal hind-limb clasping in 63% of knockout mice compared to 0% of wild-type littermates.
Absolute Event Rate: 63% vs 0%
Targeted deletion of Kcne3 in mice impairs skeletal muscle function and alters K+ channel expression, confirming its functional requirement in skeletal muscle.
Validates KCNE3 expression in skeletal muscle; leaves open functional role in human channelopathies.
KCNE3 (MiRP2) forms heteromeric voltage‐gated K + channels with the skeletal muscle‐expressed KCNC4 (K v 3.4) a subunit. KCNE3 was the first reported skeletal muscle K + channel disease gene, but the requirement for KCNE3 in skeletal muscle has been questioned. Here, we confirmed KCNE3 transcript and protein expression in mouse skeletal muscle using Kcne3 ‐/‐ tissue as a negative control. Whole‐transcript microarray analysis (770,317 probes, interrogating 28,853 transcripts) findings were consistent with Kcne3 deletion increasing gastrocnemius oxidative metabolic gene expression and the proportion of type IIa fast‐twitch oxidative muscle fibers, which was verified using immunofluorescence. The down‐regulated transcript set overlapped with muscle unloading gene expression profiles (‡1.5‐fold change; P < 0.05). Gastrocnemius K + channel a subunit remodeling arising from Kcne3 deletion was highly specific, involving just 3 of 69 a subunit genes probed: known KCNE3 partners KCNC4 and KCNH2 (mERG) were down‐regulated, and KCNK4 (TRAAK) was up‐regulated (P < 0.05). Functionally, Kcne3 ‐/‐ mice exhibited abnormal hind‐limb clasping upon tail suspension (63% of Kcne3 ‐/‐ mice ‡10‐mo‐old vs. 0% age‐matched Kcne3 +/+ littermates). Whereas 5 of 5 Kcne3 +/+ mice exhibited the typical biphasic decline in contractile force with repetitive stimuli of hind‐limb muscle, both in vivo and in vitro , this was absent in 6 of 6 Kcne3 ‐/‐ mice tested. Finally, myoblasts isolated from Kcne3 ‐/‐ mice exhibit faster‐inactivating and smaller sustained outward currents than those from Kcne3 +/+ mice. Thus, Kcne3 deletion impairs skeletal muscle function in mice.—King, E. C., Patel, V., Anand, M., Zhao, X., Crump, S. M., Hu, Z., Weisleder, N., Abbott, G. W. Targeted deletion of Kcne3 impairs skeletal muscle function in mice. FASEB J. 31, 2937–2947 (2017). www.fasebj.org
No takes yet. Share an insight, caveat, or question.
King et al. (2017) studied Skeletal muscle function. Targeted deletion of Kcne3 vs. Kcne3+/+ (wild-type) littermates was evaluated on Abnormal hind-limb clasping upon tail suspension in mice ≥10 months old. Targeted deletion of Kcne3 impaired skeletal muscle function, evidenced by abnormal hind-limb clasping in 63% of knockout mice compared to 0% of wild-type littermates.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: