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.
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