There are few detailed descriptions of the coronary arterial patterns in the mouse. Some recent reports on coronary anomalies in mutant mouse models have uncovered the importance of several genes (i.e. iv and connexin43) in coronary morphogenesis. These mutations spontaneously appeared (iv) or were generated (connexin43) in a C57BL/6 background, which is widely used for the development of mutant mice. We have studied the origin and course of the main coronary arteries of two C57BL/6 mouse strains. Unusual anatomical coronary arterial patterns were found, including: solitary ostium in aorta, accessory ostium, high take‐off, aortic intramural course, slit‐like ostium, sinus‐like ostium and origin of a septal artery from the left coronary artery. In humans, some of these conditions are clinically relevant. Most of these patterns, which differ from those observed in wild mice and Swiss albino mice, coincide with those previously found in iv/iv and connexin43 knockout mice. The results indicate that there is variability in the coronary arterial arrangement of the laboratory mouse. Care should be taken when analysing coronary phenotypes of mutant mouse models.

In the Syrian hamster, anomalies in the origin of the left coronary artery are significantly associated with the bicuspid condition of the aortic valve. In this species, bicuspid aortic valves are expressions of a trait, the variation of which takes the form of a phenotypic continuum, ranging from a tricuspid aortic valve with no commissural fusion to a bicuspid aortic valve with the aortic sinuses located in ventrodorsal orientation and devoid of any raphe. The intermediate stages of the continuum are represented by tricuspid aortic valves with a more or less extensive fusion of the ventral commissure and bicuspid aortic valves with a more or less developed raphe located in the ventral aortic sinus. The present study was designed to decide whether there is a gap between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies, or whether this incidence varies according to the different tricuspid and bicuspid morpho types of the continuum. The study was carried out in Syrian hamsters belonging to a single inbred family with a high incidence of tricuspid aortic valves with fusion of the ventral commissure, bicuspid aortic valves, and anomalies in the origin of the left coronary artery, i.e. single right coronary artery ostium in aorta, anomalous origin of the left coronary artery from the pulmonary artery, and anomalous origin of the left coronary artery from the dorsal aortic sinus. The specimens were examined by means of a stereomicroscope and, in several cases; scanning electron microscopy was also used. The relationships between anomalous coronary artery patterns and aortic valve morphologies were tested using a logistic regression model. The results obtained indicate that there is no discontinuity between tricuspid and bicuspid aortic valves regarding the incidence of coronary artery anomalies. The probability of occurrence of anomalous coronary artery patterns increases continuously according to the deviation degree of the aortic valve from its normal (tricuspid) design. The present findings suggest that in the Syrian hamster, the morphogenetic mechanisms involved in the formation of congenital anomalous aortic valves and anomalies in the origin of the left coronary artery, respectively, are strongly related from an aetiological viewpoint.

Background Congenital bicuspid and quadricuspid pulmonary valves have received little attention because of their limited clinical relevance. However, knowledge of the mechanisms by which these anomalous valves develop is essential to obtain a more accurate survey of the etiological factors implicated in the malformations of the cardiac outflow tract in mammals. The present study was designed to assess the anatomical features of bicuspid and quadricuspid pulmonary valves in Syrian hamsters as well as to elucidate the mechanisms involved in the formation of these defective valves. Methods The sample examined consisted of 206 adults and 28 embryos belonging to a laboratory-inbred family of Syrian hamsters with a high incidence of congenital anomalies of the pulmonary and aortic valves. The study was carried out using histological techniques for light microscopy, semithin sections, and scanning electron microscopy. Results The pulmonary valve was tricuspid in 140 of the 206 adult hamsters, and in 124 of these tricuspid valves the dorsal commissure was more or less extensively fused. Another 45 hamsters possessed a bicuspid pulmonary valve with the sinuses oriented ventrodorsally. In 43 of these bicuspid valves, a raphe was located in the dorsal pulmonary sinus. The pulmonary valve was quadricuspid in a further nine specimens. The remaining 12 hamsters had a tricuspid pulmonary valve with a raphe-like ridge located in the right pulmonary sinus. In seven of these valves, the dorsal commissure showed a more or less extensive fusion. The embryos examined, aged between 11 days, 3 hours and 12 days, 6 hours postcoitum, were at the beginning of the valvulogenesis. In five of the 28 embryos, the pulmonary valve consisted of three mesenchymal valve cushions, right, left, and dorsal. In a further 17 embryos, the right and left valve cushions were more or less fused toward the lumen of the pulmonary artery. In the remaining six embryos, the left and dorsal valve cushions were normal, whereas the right cushion was divided into two lobes. Conclusions The present findings suggest that in the Syrian hamster: (1) bicuspid pulmonary valves result from the extensive fusion of the right and left pulmonary valve cushions at the beginning of the valvulogenesis, (2) the partial fusion of the right and left pulmonary valve cushions leads to the formation of tricuspid pulmonary valves with a more or less extensive fusion of the dorsal commissure, (3) quadricuspid pulmonary valves result from the partition of one of the three valve cushions at a very early stage of the valvulogenesis, and (4) the partial division of the right pulmonary valve cushion may lead to the development of tricupsid pulmonary valves with a raphe-like ridge located in the right pulmonary sinus. In addition, the present findings, together with previous observations in Syrian hamsters, indicate that in this species the mechanisms by which bicuspid and quadricuspid pulmonary valves develop are similar to those by which bicuspid and quadricuspid aortic valves form, respectively. However, the primary factor or factors that induce the malformations of the pulmonary valve operate independently from those inducing the malformations of the aortic valve. Anat. Rec. 250:70–79, 1998.

The bifoliate, or bicuspid, aortic valve (BAV) is the most frequent congenital cardiac anomaly in man. It is a heritable defect, but its mode of inheritance remains unclear. Previous studies in Syrian hamsters showed that BAVs with fusion of the right and left coronary leaflets are expressions of a trait, the variation of which takes the form of a phenotypic continuum. It ranges from a trifoliate valve with no fusion of the coronary leaflets to a bifoliate root devoid of any raphe. The intermediate stages are represented by trifoliate valves with fusion of the coronary aortic leaflets, and bifoliate valves with raphes. The aim of this study was to elucidate whether the distinct morphological variants rely on a common genotype, or on different genotypes. We examined the aortic valves from 1 849 Syrian hamsters belonging to a family subjected to systematic inbreeding by full‐sib mating. The incidence of the different trifoliate aortic valve (TAV) and bifoliate aortic valve (BAV) morphological variants widely varied in the successive inbred generations. TAVs with extensive fusion of the leaflets, and BAVs, accounted for five‐sixths of the patterns found in Syrian hamsters considered to be genetically alike or virtually isogenic, with the probability of homozygosity being 0.999 or higher. The remaining one‐sixth hamsters had aortic valves with a tricuspid design, but in most cases the right and left coronary leaflets were slightly fused. Results of crosses between genetically alike hamsters, with the probability of homozygosity being 0.989 or higher, revealed no significant association between the valvar phenotypes in the parents and their offspring. Our findings are consistent with the notion that the BAVs of the Syrian hamster are expressions of a quantitative trait subject to polygenic inheritance. They suggest that the genotype of the virtually isogenic animals produced by systematic inbreeding greatly predisposes to the development of anomalous valves, be they bifoliate, or trifoliate with extensive fusion of the leaflets. We infer that the same underlying genotype may account for the whole range of valvar morphological variants, suggesting that factors other than genetic ones are acting during embryonic life, creating the so‐called intangible variation or developmental noise, and playing an important role in the definitive anatomic configuration of the valve. The clinical implication from our study is that congenital aortic valves with a trifoliate design, but with fusion of coronary aortic leaflets, may harbour the same inherent risks as those already recognised for BAVs with fusion of right and left coronary leaflets.