Evaluation of the contributions of ADAMs 9, 12, 15, 17, and 19 to heart development and ectodomain shedding of neuregulins β1 and β2 Journal Article
| Authors: | Horiuchi, K.; Zhou, H. M.; Kelly, K.; Manova, K.; Blobel, C. P. |
| Article Title: | Evaluation of the contributions of ADAMs 9, 12, 15, 17, and 19 to heart development and ectodomain shedding of neuregulins β1 and β2 |
| Abstract: | Defects in heart development are the most common congenital abnormalities in humans, providing a strong incentive to learn more about the underlying causes. Previous studies have implicated the metalloprotease-disintegrins ADAMs (a disintegrin and metalloprotease) 17 and 19 as well as heparin binding EGF-like growth factor (HB-EGF) and neuregulins in heart development in mice. Here, we show that mice lacking both ADAMs 17 and 19 have exacerbated defects in heart development compared to mice lacking either ADAM, providing the first evidence for redundant or compensatory functions of ADAMs in development. Moreover, we identified additional compensatory or redundant roles of ADAMs 9 and 19 in morphogenesis of the mitral valve and cardiac outflow tract. Cell biological studies designed to address the functions of these ADAMs in shedding of HB-EGF uncovered a contribution of ADAM19 to this process, but this was only evident in the absence of the major HB-EGF sheddase, ADAM17. In addition, ADAM17 emerged as the major sheddase for neuregulins β1 and β2 in mouse embryonic fibroblasts. These results raise the possibility that ADAMs 9, 17, and 19 contribute to heart development in humans and have implications for understanding the mechanisms underlying congenital heart disease. © 2005 Elsevier Inc. All rights reserved. |
| Keywords: | controlled study; unclassified drug; disease course; nonhuman; protein function; mouse; cytology; animals; mice; mice, knockout; animal tissue; embryo; animal experiment; nerve tissue proteins; morphogenesis; nerve growth factors; cercopithecus aethiops; cos cells; molecular mechanics; recombinant fusion proteins; evaluation; enzyme analysis; heart failure; newborn; fibroblast; fibroblasts; developmental disorder; animals, newborn; monkey; heart; myocardium; heart defects, congenital; comprehension; heart development; heparin binding epidermal growth factor; metalloproteinase; ectodomain shedding; heart ventricle septum defect; neu differentiation factor; tumor necrosis factor alpha converting enzyme; metalloprotease-disintegrin; congenital heart disease; a disintegrin and metalloprotease 12; adam; endocardial cushion; hb-egf; neuregulin; a disintegrin and metalloprotease 15; a disintegrin and metalloprotease 19; a disintegrin and metalloprotease 9; neuregulin beta1; neuregulin beta2; malrotation syndrome; mitral valve; disintegrins; metalloendopeptidases; tricuspid valve |
| Journal Title: | Developmental Biology |
| Volume: | 283 |
| Issue: | 2 |
| ISSN: | 0012-1606 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2005-07-15 |
| Start Page: | 459 |
| End Page: | 471 |
| Language: | English |
| DOI: | 10.1016/j.ydbio.2005.05.004 |
| PUBMED: | 15936750 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 69" - "Export Date: 24 October 2012" - "CODEN: DEBIA" - "Source: Scopus" |
