This mutant strain, carrying at least two mutations, 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 here. Because G1 sperm were cryopreserved, additional incidental mutations are also segregating in this strain.
Two mutant phenotypes are observed. In the first, associated with the Ccdc39 gene, homozygotes demonstrate cardiovascular defects that involve heterotaxy presenting with dextrocardia/dextroversion and a spectrum of complex congenital heart disease such as superior-inferior ventricles, overriding aorta/double outlet right ventricle (DORV), DORV Taussig Bing subtype, transposition of the great arteries (TGA), atrioventricular septal defect (AVSD), perimembranous and muscular ventricular septal defects (VSD), interrupted aortic arch (IAA), aberrant left subclavian artery forming incomplete vascular ring and dual inferior vena cava (IVC), and right/left atrial isomerism. Abnormal thoracic and abdominal organ situs anomalies, such as dextrogastria/midline stomach, hypoplastic spleen/asplenia, left lung isomerism, and midline liver are also seen. Airway cilia are immotile.
In the second phenotype (associated with b2b2025.2Clo), cardiovascular defects involve double outlet right ventricle (DORV), hypoplastic pulmonary artery, atrioventricular septal defect (AVSD), right aortic arch (RAA), ventricular non-compaction, and aberrant left subclavian artery forming incomplete vascular ring. Right microphthalmia and syndactyly are also seen.
