CALCIUM HANDLING IN THE SPLOTCH (SP2H) MOUSE MUTANT

描述(改编自申请人的摘要)：分子 模型突变小鼠圆锥干心脏缺陷的特征 提出了Splotch(Sp2H)。这个突变体是由于Pax3的缺陷造成的 基因，一个已知的DNA结合同源结构域。Sp2H小鼠表现出永久性主干 动脉粥样硬化(PTA)，一种预计不会导致宫内的异常 死亡。然而，携带PTA的Sp2H突变小鼠大约在第14天死亡 个人电脑。初步数据显示，除了结构异常，Sp2H 小鼠在兴奋-收缩耦合方面存在缺陷。此外，还分析了 纯合子突变小鼠的钙通道表现出增加 Alpha1C亚基，相对于其他亚基。申请者假设 具有PTA基因突变的Sp2H小鼠在编码基因上存在异常 对钙向细胞内的运输非常重要的蛋白质。

DESCRIPTION (adapted from the applicant's abstract): Molecular characterization of conotruncal heart defects in the model mutant mouse splotch (Sp2H) are proposed. This mutant is due to a defect in the Pax3 gene, a known DNA-binding homeodomain. Sp2H mice exhibit persistent truncus arteriosus (PTA), an anomaly that is not predicted to cause intrauterine death. Yet 100% of Sp2H mutant mice with PTA die at approximately day 14 pc. Preliminary data suggest that in addition to structural anomalies, Sp2H mice have a defect in excitation-contraction coupling. Further, analyses of calcium channels in homozygous mutant mice demonstrate an increase in the alpha1C subunit, relative to other subunits. The applicant hypothesizes that Sp2H mouse mutants with PTA have an abnormality in the genes encoding proteins that are important for transport of calcium into cells.