Kcnma1-tdtomato floxed allele sequence

BK large conductance calcium-activated K+ channels (KCa1.1) are expressed widely across many tissues, contributing to systemic regulation of cardiovascular, neurological, and other specialized physiological functions. The pore-forming α subunit is encoded by the Kcnma1 gene, originally named mSlo1 in mouse and slowpoke in Drosophila. Global deletion in mouse (Kcnma1−/−) produces a plethora of defects in neuron and muscle excitability, as well as other phenotypes related to channel function in nonexcitable cells. While homozygous null mice are viable, the ubiquitous loss of BK function has complicated the interpretation of phenotypes involving the interaction of multiple cell types which independently express BK channels. Here, we report the generation of a targeted allele for conditional inactivation of Kcnma1 using the Cre-loxP system (Kcnma1fl-tdTomato). Cre-mediated recombination generates a null allele, and BK currents were not detectable in neurons and muscle cells from Nestin-Cre;...

大电导钙激活钾通道（BK large conductance calcium-activated K+ channels，KCa1.1）在多种组织中广泛表达，参与心血管、神经系统及其他特化生理功能的全身性调控。其孔形成α亚基由Kcnma1基因编码，该基因最初在小鼠中被命名为mSlo1，在果蝇（Drosophila）中被命名为slowpoke。对小鼠进行全身性Kcnma1基因敲除（Kcnma1−/−）会导致神经元与肌肉兴奋性出现诸多异常，同时还会引发非兴奋性细胞中与该通道功能相关的其他表型。尽管纯合敲除小鼠可存活，但BK功能的全身性缺失极大增加了解析涉及多种独立表达BK通道的细胞类型相互作用的表型的难度。本研究报道了一种利用Cre-loxP重组系统实现Kcnma1条件性失活的靶向等位基因（Kcnma1fl-tdTomato）。经Cre介导的重组可产生无效等位基因，且在Nestin-Cre;……的神经元与肌肉细胞中无法检测到BK电流。