BACKGROUND: Transforming growth factor-beta(2) (TGF-beta(2)) is a member of a family of growth factors with the potential to modify multiple processes. Mice deficient in the TGF-beta(2) gene die around birth and show a variety of defects of different organs, including the heart. METHODS AND RESULTS: We studied the hearts of TGF-beta(2)-null mouse embryos from 11.5 to 18.5 days of gestation to analyze the types of defects and determine which processes of cardiac morphogenesis are affected by the absence of TGF-beta(2). Analysis of serial sections revealed malformations of the outflow tract (typically a double-outlet right ventricle) in 87.5%. There was 1 case of common arterial trunk. Abnormal thickening of the semilunar valves was seen in 4.2%. Associated malformations of the atrioventricular (AV) canal were found in 62.5% and were composed of perimembranous inlet ventricular septal defects (37.5%), AV valve thickening (33.3%), overriding tricuspid valve (25.0%), and complete AV septal defects (4.2%). Anomalies of the aorta and its branches were seen in 33.3%. Immunohistochemical staining showed failure of myocardialization of the mesenchyme of the atrial septum and the ventricular outflow tract as well as deficient valve differentiation. Morphometry documented this to be associated with absence of the normal decrease of total endocardial cushion volume in the older stages. Apoptosis in TGF-beta(2)-knockout mice was increased, although regional distribution was normal. CONCLUSIONS: TGF-beta(2)-knockout mice exhibited characteristic cardiovascular anomalies comparable to malformations seen in the human population.
BACKGROUND:Transforming growth factor-beta(2) (TGF-beta(2)) is a member of a family of growth factors with the potential to modify multiple processes. Mice deficient in the TGF-beta(2) gene die around birth and show a variety of defects of different organs, including the heart. METHODS AND RESULTS: We studied the hearts of TGF-beta(2)-null mouse embryos from 11.5 to 18.5 days of gestation to analyze the types of defects and determine which processes of cardiac morphogenesis are affected by the absence of TGF-beta(2). Analysis of serial sections revealed malformations of the outflow tract (typically a double-outlet right ventricle) in 87.5%. There was 1 case of common arterial trunk. Abnormal thickening of the semilunar valves was seen in 4.2%. Associated malformations of the atrioventricular (AV) canal were found in 62.5% and were composed of perimembranous inlet ventricular septal defects (37.5%), AV valve thickening (33.3%), overriding tricuspid valve (25.0%), and complete AV septal defects (4.2%). Anomalies of the aorta and its branches were seen in 33.3%. Immunohistochemical staining showed failure of myocardialization of the mesenchyme of the atrial septum and the ventricular outflow tract as well as deficient valve differentiation. Morphometry documented this to be associated with absence of the normal decrease of total endocardial cushion volume in the older stages. Apoptosis in TGF-beta(2)-knockout mice was increased, although regional distribution was normal. CONCLUSIONS:TGF-beta(2)-knockout mice exhibited characteristic cardiovascular anomalies comparable to malformations seen in the human population.
Authors: Thomas Doetschman; Joey V Barnett; Raymond B Runyan; Todd D Camenisch; Ronald L Heimark; Henk L Granzier; Simon J Conway; Mohamad Azhar Journal: Cell Tissue Res Date: 2011-09-28 Impact factor: 5.249
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Authors: Wenlai Zhou; Lizhu Lin; Arindam Majumdar; Xue Li; Xiaoxue Zhang; Wei Liu; Leah Etheridge; Yunqing Shi; James Martin; Wim Van de Ven; Vesa Kaartinen; Anthony Wynshaw-Boris; Andrew P McMahon; Michael G Rosenfeld; Sylvia M Evans Journal: Nat Genet Date: 2007-09-02 Impact factor: 38.330
Authors: Kai Jiao; Holger Kulessa; Kevin Tompkins; Yingna Zhou; Lorene Batts; H Scott Baldwin; Brigid L M Hogan Journal: Genes Dev Date: 2003-09-15 Impact factor: 11.361
Authors: Christian Grütter; Trevor Wilkinson; Richard Turner; Sadhana Podichetty; Donna Finch; Matthew McCourt; Scott Loning; Lutz Jermutus; Markus G Grütter Journal: Proc Natl Acad Sci U S A Date: 2008-12-10 Impact factor: 11.205