Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse.

Abstract

BACKGROUND In the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies. METHODS AND RESULTS The morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion; the morphological types were similar to those seen in human cases. Of cases with either usual or mirror-image arrangement of the appendages, 33.2% had abnormal spleens, but only 3.1% had cardiac defects. Similarly, venous abnormalities were much more common (30.1%) than cardiac defects. CONCLUSIONS Study results endorse the importance of the morphology of atrial appendages in predicting cardiac abnormalities and point to the marked inconsistency of the arrangement of other organs, including the spleen and the connections of the systemic veins.

Cardiopulmonary malformations in the inv/inv mouse

“…The iv/iv phenotype is the result of loss-of-function mutations in the L-R dynein gene (Supp et al, 1999). The iv/iv mice display truly randomized situs of thoracic and abdominal viscera and have frequent cardiac abnormalities, findings very similar to the human malformation syndromes diagnosed as heterotaxies (Seo et al, 1992;Icardo and Sanchez de Vega, 1991). Moreover, the cardiac abnormalities identified in iv/iv mice are in general compatible with human heterotaxy cardiac abnormalities.…”

Suppression of atrial myosin gene expression occurs independently in the left and right ventricles of the developing mouse heart

“…The iv mouse carries an autosomal recessive mutation in the left/right-dynein gene (Supp et al, 1997) which results in the loss of embryonic left/right positional information and randomisation of the direction of cardiac looping (Layton, 1976). iv/iv embryos also display an elevated frequency of cardiac malformations (Icardo and Sanchez de Vega, 1991;Seo et al, 1992). In this study, hearts were designated as situs inversus if the morphological right (pulmonary) ventricle and OFT were positioned on the left-hand side of the heart.…”

Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development.

“…In the absence of laterality signals, a stochastic event may otherwise determine its looping direction. In contrast, however, a whole spectrum of cardiac abnormalities results from defects in laterality (Burn 1991;Seo et al 1992;Bowers et al 1996), suggesting that establishment of asymmetry in the heart is often unsuccessful and that situs can be ambiguous. Because these cardiac defects are mostly serious and/or fatal, understanding the mechanism of looping is a central issue in cardiac biology.…”