ADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesisReport as inadecuate

ADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis - Download this document for free, or read online. Document in PDF available to download.


, Volume 19, Issue 1, pp 53–65

First Online: 07 October 2015Received: 07 May 2015Accepted: 28 September 2015DOI: 10.1007-s10456-015-9488-z

Cite this article as: Janssen, L., Dupont, L., Bekhouche, M. et al. Angiogenesis 2016 19: 53. doi:10.1007-s10456-015-9488-z


The only documented activity of a subclass of ADAMTS proteases comprising ADAMTS2, 3 and 14 is the cleavage of the aminopropeptide of fibrillar procollagens. A limited number of in vitro studies suggested that ADAMTS3 is mainly responsible for procollagen II processing in cartilage. Here, we created an ADAMTS3 knockout mouse Adamts3 model to determine in vivo the actual functions of ADAMTS3. Heterozygous Adamts3 mice were viable and fertile, but their intercrosses demonstrated lethality of Adamts3 embryos after 15 days of gestation. Procollagens I, II and III processing was unaffected in these embryos. However, a massive lymphedema caused by the lack of lymphatics development, an abnormal blood vessel structure in the placenta and a progressive liver destruction were observed. These phenotypes are most probably linked to dysregulation of the VEGF-C pathways. This study is the first demonstration that an aminoprocollagen peptidase is crucial for developmental processes independently of its primary role in collagen biology and has physiological functions potentially involved in several human diseases related to angiogenesis and lymphangiogenesis.

KeywordsADAMTS Lymphangiogenesis Angiogenesis Collagen Placenta Development Lauriane Janssen and Laura Dupont have contributed equally to this work.

Johanne Dubail and Alain Colige have promoted and supervised equally this work.

Electronic supplementary materialThe online version of this article doi:10.1007-s10456-015-9488-z contains supplementary material, which is available to authorized users.

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Author: Lauriane Janssen - Laura Dupont - Mourad Bekhouche - Agnès Noel - Cédric Leduc - Marianne Voz - Bernard Peers - Didier C


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