Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.
Adamts18 deletion results in distinct developmental defects and provides a model for congenital disorders of lens, lung, and female reproductive tract development.
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ADAMTS18缺失导致不同的发育缺陷，并为晶状体，肺和女性生殖道发育的先天性疾病提供了模型。
DOI：
10.1242/bio.019711
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发表时间：
2016-11-15
期刊：
影响因子：
2.4
通讯作者：
Brisken C
中科院分区：
文献类型：
--
作者：
Ataca D;Caikovski M;Piersigilli A;Moulin A;Benarafa C;Earp SE;Guri Y;Kostic C;Arsenijevic Y;Soininen R;Apte SS;Brisken C
ADAMTS家族由19种分泌的金属蛋白酶组成，它们裂解细胞外基质成分，在许多疾病和生理环境中具有不同的功能。它们中的许多仍然是孤立的蛋白水解酶，其中包括ADAMTS18，它与发育性眼睛疾病、血小板功能和各种恶性肿瘤有关。为了评估ADAMTS18的体内功能，我们产生了一个含有灭活的ADAMTS18等位基因的小鼠品系。在C57BL6/Ola背景下，Adamts18缺陷小鼠以正常的孟德尔比例出生，并能存活，但表现出一过性的生长延迟。组织学检查显示100%的穿透性眼部缺陷是由于晶状体材料通过晶状体囊膜渗漏造成的，发生在胚胎13.5天，此时晶状体生长迅速。成人18缺陷肺表现为细支气管性分支改变。50%的突变女性是不育的，因为阴道梗阻是由于阴道背腹隔或阴道闭锁造成的。在突变的小鼠品系中，卵巢网状病毒的发生率增加。因此，Adamts18在不同组织的发育中是必不可少的，新的小鼠品系可能有助于研究ADAMTS18在人类疾病中的功能，特别是在不孕不育和癌症发生的背景下。摘要：我们培育的小鼠缺乏与人类疾病有关的分泌型蛋白酶ADAMTS18，并表明该基因在晶状体、肺部和雌性生殖道的发育中是必需的。
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. Summary: We generated mice deficient for the secreted protease ADAMTS18 implicated in human disease and show that the gene is required in the development of the lens, lung, and the female reproductive tract.
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DOI：
10.1152/ajplung.00181.2013
发表时间：
2013-12-01
影响因子：
4.9
作者：
Cremona, Tiziana P.;Tschanz, Stefan A.;Benarafa, Charaf
通讯作者：
Benarafa, Charaf
影响因子：
3.7
作者：
Peluso I;Conte I;Testa F;Dharmalingam G;Pizzo M;Collin RW;Meola N;Barbato S;Mutarelli M;Ziviello C;Barbarulo AM;Nigro V;Melone MA;European Retinal Disease Consortium;Simonelli F;Banfi S
通讯作者：
Banfi S
影响因子：
12.3
作者：
Kelwick R;Desanlis I;Wheeler GN;Edwards DR
通讯作者：
Edwards DR
影响因子：
11.8
作者：
McCulloch, Daniel R.;Nelson, Courtney M.;Dixon, Laura J.;Silver, Debra L.;Wylie, James D.;Lindner, Volkhard;Sasaki, Takako;Cooley, Marion A.;Argraves, W. Scott;Apte, Suneel S.
通讯作者：
Apte, Suneel S.
影响因子：
1.5
作者：
Long, GG
通讯作者：
Long, GG