Increased fibronectin deposition in embryonic hearts of retinol-binding protein-null mice. Circ Res 2003 May 02;92(8):920-8
Date
03/29/2003Pubmed ID
12663486Pubmed Central ID
PMC3752713DOI
10.1161/01.RES.0000069030.30886.8FScopus ID
2-s2.0-0038304602 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
Precise regulation of retinoid levels is critical for normal heart development. Retinol-binding protein (RBP), an extracellular retinol transporter, is strongly secreted by cardiogenic endoderm. This study addresses whether RBP gene ablation affects heart development. Despite exhibiting an >85% decrease in serum retinol, adult RBP-null mice are viable, breed, and have normal vision when maintained on a vitamin A-sufficient diet. Comparison of RBP-null with wild-type (WT) hearts from embryos at day 9.0 (E9.0) through E12.5 revealed an RBP-null phenotype similar to that of other retinoid-deficient models. At an early stage, RBP-null hearts display retarded trabecular development, which recovers by E9.5. This is accompanied at E9.5 and E10.5 by precocious differentiation of subepicardial cardiac myocytes. Most remarkably, RBP-null hearts display augmented deposition of fibronectin protein in the cardiac jelly at E9.0 through E10.5 and in the outflow tract at E12.5. This phenomenon, which was detected by immunohistochemistry and Western blotting without increased fibronectin transcript levels, is accompanied by increased numbers of mesenchymal cells in the outflow tract but not in the atrioventricular canal. RBP-null cardiac myocytes, especially in the subepicardial layer, display increased cell proliferation. This phenotype may present a model of subclinical retinoid insufficiency characterized by alteration of an extracellular matrix component and altered cellular differentiation and proliferation, changes that may have functional consequences for adult cardiac function. This murine model may have relevance to fetal development in human populations with inadequate retinoid intake.
Author List
Wendler CC, Schmoldt A, Flentke GR, Case LC, Quadro L, Blaner WS, Lough J, Smith SMAuthor
John W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBlotting, Northern
Blotting, Western
Cell Division
Embryo, Mammalian
Female
Fibronectins
Gene Expression Regulation, Developmental
Heart
In Situ Hybridization
Male
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Mice, Knockout
Myocardium
RNA, Messenger
Retinol-Binding Proteins
Time Factors
