例如:"lncRNA", "apoptosis", "WRKY"

Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development.

Dis Model Mech. 2016 Apr 1;9(4):413-25. Epub 2016 Jan 28
Maria E Baardman 1 , Mathijs V Zwier 2 , Lambertus J Wisse 3 , Adriana C Gittenberger-de Groot 3 , Wilhelmina S Kerstjens-Frederikse 1 , Robert M W Hofstra 4 , Angelika Jurdzinski 2 , Beerend P Hierck 3 , Monique R M Jongbloed 5 , Rolf M F Berger 6 , Torsten Plösch 7 , Marco C DeRuiter 8
Maria E Baardman 1 , Mathijs V Zwier 2 , Lambertus J Wisse 3 , Adriana C Gittenberger-de Groot 3 , Wilhelmina S Kerstjens-Frederikse 1 , Robert M W Hofstra 4 , Angelika Jurdzinski 2 , Beerend P Hierck 3 , Monique R M Jongbloed 5 , Rolf M F Berger 6 , Torsten Plösch 7 , Marco C DeRuiter 8
+ et al

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Author information
  • 1 Department of Genetics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
  • 2 Department of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
  • 3 Department of Anatomy and Embryology, Leiden University Medical Center, PO-Box 9600, Leiden 2300 RC, The Netherlands.
  • 4 Department of Clinical Genetics, Erasmus Medical Center Rotterdam, PO-Box 2040, Rotterdam 3000 CA, The Netherlands Neural Development and Gastroenterology Units, UCL Institute of Child Health, London WC1 NEH, UK.
  • 5 Department of Cardiology and Department of Anatomy and Embryology, Leiden University Medical Center, PO-Box 9600, Leiden 2300 RC, The Netherlands.
  • 6 Center for Congenital Heart Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
  • 7 Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, Groningen 9713 GZ, The Netherlands.
  • 8 Department of Anatomy and Embryology, Leiden University Medical Center, PO-Box 9600, Leiden 2300 RC, The Netherlands m.c.deruiter@lumc.nl.
全文

摘要


Lipoprotein-related receptor protein 2 (LRP2) is important for development of the embryonic neural crest and brain in both mice and humans. Although a role in cardiovascular development can be expected, the hearts ofLrp2knockout (KO) mice have not yet been investigated. We studied the cardiovascular development ofLrp2KO mice between embryonic day 10.5 (E10.5) and E15.5, applying morphometry and immunohistochemistry, using antibodies against Tfap2α (neural crest cells), Nkx2.5 (second heart field), WT1 (epicardium derived cells), tropomyosin (myocardium) and LRP2. TheLrp2KO mice display a range of severe cardiovascular abnormalities, including aortic arch anomalies, common arterial trunk (persistent truncus arteriosus) with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve and marked thinning of the ventricular myocardium. Both the neural crest cells and second heart field, which are essential for the lengthening and growth of the right ventricular outflow tract, are abnormally positioned in theLrp2KO. This explains the absence of the aorto-pulmonary septum, which leads to common arterial trunk and ventricular septal defects. Severe blebbing of the epicardial cells covering the ventricles is seen. Epithelial-mesenchymal transition does occur; however, there are fewer WT1-positive epicardium-derived cells in the ventricular wall as compared to normal, coinciding with the myocardial thinning and deep intertrabecular spaces. LRP2 plays a crucial role in cardiovascular development in mice. This corroborates findings of cardiac anomalies in humans withLRP2mutations. Future studies should reveal the underlying signaling mechanisms in which LRP2 is involved during cardiogenesis.

KEYWORDS: Cardiac outflow tract, Heart development, Lipoprotein-related receptor protein 2, Neural crest, Second heart field