This T-to-A point mutation in the Mmp21 (matrix metallopeptidase 21) cDNA was identified in an ENU screen for recessive cardiovascular development phenotypes in Dr. Cecilia Lo's laboratory, NHLBI Cardiovascular Development Consortium (CvDC). It was recovered from G1 sperm and associated with the phenotype described described here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.
Homozygotes demonstrate complex congenital heart disease associated with heterotaxy, such as dextrocardia, double outlet right ventricle (DORV) or DORV Taussig-Bing subtype, transposition of the great arteries (TGA), atrioventricular septal defect (AVSD), superior-inferior ventricles, and hypoplastic right ventricle (RV). Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria, right pulmonary isomerism, malaligned sternal vertebrae, and inverted liver lobation are also seen. Micrognathia is also observed.