Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.

Ataca, Dalya; Caikovski, Marian; Piersigilli, Alessandra; Moulin, Alexandre; Benarafa, Charaf; Earp, Sarah E; Guri, Yakir; Kostic, Corinne; Arsenijvic, Yvan; Soininen, Raija; Apte, Suneel S; Brisken, Cathrin (2016). Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development. Biology open BiO, 5(11), pp. 1585-1594. Company of Biologists 10.1242/bio.019711

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
04 Faculty of Medicine > Other Institutions > Teaching Staff, Faculty of Medicine

UniBE Contributor:

Benarafa, Charaf

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2046-6390

Publisher:

Company of Biologists

Language:

English

Submitter:

Ursula Zingg-Zünd

Date Deposited:

22 May 2017 14:22

Last Modified:

24 May 2017 15:16

Publisher DOI:

10.1242/bio.019711

PubMed ID:

27638769

Uncontrolled Keywords:

Adamts18; Lens capsule; Lung development; Metalloproteinase; Rete ovary; Vaginal septum

BORIS DOI:

10.7892/boris.95402

URI:

https://boris.unibe.ch/id/eprint/95402

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