Spectrum of heart malformations in mice with situs solitus, situs inversus, and associated visceral heterotaxy.

BACKGROUND: We present a study of the heart malformations found in a collection of mouse fetuses of the iv/iv strain between days 16.5 and 18.5 of gestation.

METHODS AND RESULTS: One hundred hearts were serially sectioned and studied by segmental analysis with a light microscope. Forty additional hearts were analyzed with a scanning microscope. Forty percent of the hearts were found to be malformed. The most frequently occurring heart malformations were persistence of the sinus venosus (9%), common atrium (17%), common atrioventricular canal (24%), double-outlet right ventricle (12%), Fallot's tetralogy (8%), and transposition of the great arteries (5%). These malformations do not usually occur in isolation but rather appear in the formation of complex cardiopathies. The most severe and frequent is the combination of persistence of sinus venosus, common atrium, common atrioventricular canal, and double-outlet right ventricle; this is the "bulboventricular heart." The morphology of each lesion, as well as the degree of association, is similar to that found in human hearts with complex cardiopathies. Some of these cardiopathies appear to be directly related to formation of the cardiac loop. The iv/iv mouse appears to constitute an excellent model with which to study the etiology and pathogenesis of complex heart defects in humans. These hearts show a high phenotypic variability in the presentation of heart lesions. From a genetic viewpoint, there is a basic defect--the bulboventricular heart--which can be considered congenital. The other malformations can be considered formes frustes of the defect type.

CONCLUSIONS: The iv gene is a developmental gene that affects basic developmental mechanisms. In this regard, heart lesions may not be the primary result of the abnormal gene activity but rather are secondary to defective interactions during cardiac development.