Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development
Dalya Ataca,
Marian Caikovski,
Alessandra Piersigilli,
Alexandre Moulin,
Charaf Benarafa,
Sarah E. Earp,
Yakir Guri,
Corinne Kostic,
Yvan Arsenivic,
Raija Soininen,
Suneel S. Apte,
Cathrin Brisken
Affiliations
Dalya Ataca
Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland
Marian Caikovski
Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland
Alessandra Piersigilli
Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland
Alexandre Moulin
Jules-Gonin Eye Hospital, University of Lausanne, Avenue de France 15, Lausanne CH-1004, Switzerland
Charaf Benarafa
Theodor Kocher Institute, University of Bern, Freiestrasse 1, Bern CH-3012, Switzerland
Sarah E. Earp
Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195, USA
Yakir Guri
Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland
Corinne Kostic
Jules-Gonin Eye Hospital, University of Lausanne, Avenue de France 15, Lausanne CH-1004, Switzerland
Yvan Arsenivic
Jules-Gonin Eye Hospital, University of Lausanne, Avenue de France 15, Lausanne CH-1004, Switzerland
Raija Soininen
Department of Pathology, Biocenter Oulu, University of Oulu, Oulu FIN-90014, Finland
Suneel S. Apte
Biomedical Engineering-ND20, Cleveland Clinic Lerner Research Institute, 9500 Euclid Ave., Cleveland, OH 44195, USA
Cathrin Brisken
Ecole Polytechnique Fédérale de Lausanne, ISREC, NCCR Molecular Oncology, Station 19, Lausanne CH-1015, Switzerland
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.
