The Kcnab2 gene encodes a beta subunit of voltage-gated potassium channels, which are important for regulating electrical signaling in neurons, cardiac cells, and muscle cells through ion channel modulation. The systemic Kvβ2 knock-out (KO) mice have a defect in life span, sporadic seizures, swim-induced tremors, and reduced body weight along with reduced skeletal muscle size, loss of immune infiltration, and defective cell proliferation. The effects of systemic Kvβ2 KO are so systemic that a cell type and time-specific Kvβ2-KO model mice are necessary to dissect the skeletal muscle development, regeneration, and cardiac functions.
Our researcher has invented a new Kcnab2 exon 4-floxed mice, suitable for experimental models to study muscle development, regeneration, and pathogenesis without significant changes in the brain and heart of TAM IP-KO mice. Kcnab2 exon 4 floxed mice were successfully generated using CRISPR/Cas9 technologies, and the conditional inactivation of Kcnab2 exon 4 in skeletal muscle was achieved by intraperitoneal injection of tamoxifen. This Kvβ2-KO was not affected systemically such as body weight, muscle weight, sexual activity, and daily behavioral activity but resulted in dramatically altered physiological and electrophysiological properties. Altogether, Kvβ2 plays a regulating role in skeletal muscle and cardiac functions in mice. Instead of the systematic deletion of Kvβ2, these Kcnab2 exon 4-floxed mice and cell type specific-Cre mice are suitable experimental models for studying muscle development.
Figure-1. Decreased Kvβ2 expression in ACE/KF double transgenic mice, with conditional Kcnab2 knockout and α-skeletal actin promoter-Cre expression.
The mRNA of Kcnab2 was detected robustly in the brain but relatively low in the tibialis anterior (TA) of wild-type mice (Fig. A & C). In TAM IP-KO mice, The Kcanb2 transcripts in the TA muscle are significantly decreased but no significant change in the brain and heart is detected (Fig. B & C). Abbreviation: T, wild-type; KO, knock-out; TA, tibialis muscle; Br, brain; Veh, vehicle; TAM, tamoxifen; IP, intraperitoneal; M, molecular marker.