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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060104-05
Application #
6537380
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Program Officer
Schramm, Charlene A
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
5
Fiscal Year
2002
Total Cost
$102,200
Indirect Cost
Name
Medical College of Georgia (MCG)
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912
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Zanin, M K; Bundy, J; Ernst, H et al. (1999) Distinct spatial and temporal distributions of aggrecan and versican in the embryonic chick heart. Anat Rec 256:366-80