title: Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.
abstract: The ADAMTS family comprises 19 secreted metalloproteinases that cleave extracellular matrix components and have diverse functions in numerous disease and physiological contexts. A number of them remain 'orphan' proteases and among them is ADAMTS18, which has been implicated in developmental eye disorders, platelet function and various malignancies. To assess in vivo function of ADAMTS18, we generated a mouse strain with inactivated Adamts18 alleles. In the C57Bl6/Ola background, Adamts18-deficient mice are born in a normal Mendelian ratio, and are viable but show a transient growth delay. Histological examination revealed a 100% penetrant eye defect resulting from leakage of lens material through the lens capsule occurring at embryonic day (E)13.5, when the lens grows rapidly. Adamts18-deficient lungs showed altered bronchiolar branching. Fifty percent of mutant females are infertile because of vaginal obstruction due to either a dorsoventral vaginal septum or imperforate vagina. The incidence of ovarian rete is increased in the mutant mouse strain. Thus, Adamts18 is essential in the development of distinct tissues and the new mouse strain is likely to be useful for investigating ADAMTS18 function in human disease, particularly in the contexts of infertility and carcinogenesis.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland.
authors.forename: Dalya
authors.initials: D
authors.lastname: Ataca
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland.
authors.forename: Marian
authors.initials: M
authors.lastname: Caikovski
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Piersigilli
authors.affiliation: Jules-Gonin Eye Hospital, University of Lausanne, Avenue de France 15, Lausanne CH-1004, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Moulin
authors.affiliation: Theodor Kocher Institute, University of Bern, Freiestrasse 1, Bern CH-3012, Switzerland.
authors.forename: Charaf
authors.initials: C
authors.lastname: Benarafa
authors.affiliation: Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Earp
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland.|Biozentrum, University of Basel, Basel CH-4056, Switzerland.
authors.forename: Yakir
authors.initials: Y
authors.lastname: Guri
authors.affiliation: Jules-Gonin Eye Hospital, University of Lausanne, Avenue de France 15, Lausanne CH-1004, Switzerland.
authors.forename: Corinne
authors.initials: C
authors.lastname: Kostic
authors.affiliation: Jules-Gonin Eye Hospital, University of Lausanne, Avenue de France 15, Lausanne CH-1004, Switzerland.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Arsenijevic
authors.affiliation: Department of Pathology, Biocenter Oulu, University of Oulu, Oulu FIN-90014, Finland.
authors.forename: Raija
authors.initials: R
authors.lastname: Soininen
authors.affiliation: Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Suneel S
authors.initials: SS
authors.lastname: Apte
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland cathrin.brisken@epfl.ch.
authors.forename: Cathrin
authors.identifier: 0000-0002-6857-3230
authors.initials: C
authors.lastname: Brisken
keywords: Adamts18; Lens capsule; Lung development; Metalloproteinase; Rete ovary; Vaginal septum