Figure 4. Homozygous Anks6^Strkr and Nek8^Roc mutants exhibit a ciliopathy syndrome.

a–i – Homozygous Anks6^Strkr mutants exhibit a spectrum of left-right patterning defects and complex CHD. a – Situs solitus, b – situs inversus and c – situs ambiguus or heterotaxy presentations in homozygous Anks6^Strkr mutant mice. Note the presence of dextrocardia with right-sided stomach in the heterotaxy mutant. d – In a heterotaxy mutant, the aorta is transposed anterior to the pulmonary artery, yielding TGA. Also, note duplication of the inferior vena cava (IVC). e – Heterotaxy mutants typically exhibit right pulmonary isomerism with four lung lobes bilaterally. f–i – Histology and 3D reconstruction using ECM allowed detailed interrogation of intracardiac anatomy for CHD diagnosis. Shown are Anks6^Strkr mutants exhibiting TGA with aorta inserted into the RV (f); atrioventricular septal defects (AVSD) (g); right atrial isomerism with symmetrical insertion of the superior vena cava (RSVC, LSVC in h) into the left and right atria, respectively, and abnormal duplication of the IVC (i), and right pulmonary isomerism with four lung lobes bilaterally (i). j–o – Homozygous Nek8^Roc mutants exhibit a spectrum of left-right patterning defects including situs inversus (j) and heterotaxy (k). l – A mutant is shown exhibiting thoracic situs with left pulmonary isomerism, as indicated by only one right and left lung lobe. m – Duplicated IVC can also be observed. n, o – Histological analysis with ECM showed double outflow right ventricle with positioning of both the aorta (Ao) and pulmonary artery (PA) over the RV (n) and a large ventricular septal defect (VSD). Also observed is an atrioventricular septal defect (AVSD in panel o). Black scale bars: 200 µm; white scale bars: 500 µm.