Atrial septal defect in cyanotic CL/Fr mice

It is widely known that some newborn CL/Fr mice with cleft lip and palate (CLP) also have cyanotic symptoms, which have been thought to depend on an atrial septal defect (ASD). In a previous study, we found that cyanotic mice tended to have more severe types of CLP. We hypothesize that the mechanical airway obstruction due to a poorly developed palatal shelf and unmoved tongue in CLP(+) mice might be related to the occurrence of cyanosis. The purpose of this study was to examine the relationships between ASD and cyanosis in CLP(+) newborns.

The newborn hearts from CLP(-), noncyanotic CLP(+), cyanotic CLP(+), CL/Fr mice and ICR mice were examined histologically, and the incidence and size of ASD was determined on neonatal day (ND) 0. In CLP(-) newborns, similar procedures were performed from ND 1 to ND 4. Furthermore, in CLP(+) newborns, development of the palatal shelf was examined.

While all the ICR mice had a well-developed atrial septum, and the incidence of ASD was 0%, about 80% of CL/Fr mice had ASD, irrespective of the presence or absence of CLP and cyanosis. On ND 0, the septum primum was significantly shorter in cyanotic CLP(+) mice than in CLP(-) mice. It also tended to be shorter in CLP(+) mice than in CLP(-) mice. Between the cyanotics and noncyanotics, there were no significant differences in the incidences of ASD and the rate of septal development. In CLP(-) mice, the septum primum developed well later and no ASD was observed on ND 4. Cyanotic newborns had significantly less developed palatal shelves than did noncyanotics.

Cyanosis may not be related to ASD and the rate of septal development, but may be related to the occurrence of CLP in this strain. Furthermore, we confirmed that some relationship exists between the development of the palatal shelf and cyanosis. The present study supports our hypothesis concerning the cause of cyanosis in CL/Fr mice.