Sox4-deficiency syndrome in mice is an animal model for common trunk.
Embryonic mice lacking functional Sox4 transcription factor die from cardiac failure at embryonic day (ED) 14. Heart morphogenesis in these embryos was analyzed in hematoxylin-azophlochsin or immunohistochemically stained, 3-dimensionally reconstructed serial sections between ED12 and ED14. Although Sox4 is expressed in the endocardially derived tissue of both the outflow tract and atrioventricular canal, Sox4-deficient hearts only suffer from defective transformation of the endocardial ridges into semilunar valves and from lack of fusion of these ridges, usually resulting in common trunk, although the least affected hearts should be classified as having a large infundibular septal defect. The more serious cases are, in addition, characterized by an abnormal number and position of the semilunar valve-leaflet anlagen, a configuration of the ridges typical for transposition of the great arteries (with linear rather than spiral course of both ridges and posterior position of the pulmonary trunk at the level of the valve), and variable size of the aorta relative to the pulmonary trunk. The coronary arteries always originated from the aorta, irrespective of its position relative to the pulmonary trunk. The restriction of the malformations to the arterial pole implies that the interaction between the endocardially derived tissue of the outflow tract and the neural crest-derived myofibroblasts determines proper development of the arterial pole.
Ya
J
J
Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, and the Department of Immunology, University of Utrecht, The Netherlands.
Schilham
M W
MW
de Boer
P A
PA
Moorman
A F
AF
Clevers
H
H
Lamers
W H
WH
D000199:Actins / Q000235:genetics; D000818:Animals; D001021:Aortic Valve / Q000002:abnormalities / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics; D003893:Desmin / Q000235:genetics; D004195:Disease Models, Animal; D005353:Fibronectins / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D006609:High Mobility Group Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000235:genetics; D050778:NFATC Transcription Factors; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D011664:Pulmonary Valve / Q000002:abnormalities / Q000196:embryology; D012333:RNA, Messenger / Q000235:genetics; D055751:SOXC Transcription Factors; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014188:Transposition of Great Vessels / Q000503:physiopathology*
D000199:Actins; D004268:DNA-Binding Proteins; D003893:Desmin; D005353:Fibronectins; D006609:High Mobility Group Proteins; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D055751:SOXC Transcription Factors; C489990:Sox4 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D018995:Myosin Heavy Chains