Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues.

Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues.
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DOI:
10.1002/dvdy.159
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发表时间:
2020-06
期刊:
Developmental dynamics : an official publication of the American Association of Anatomists
影响因子:
--
通讯作者:
Miner JH
Miner JH
中科院分区:
其他
文献类型:
--
作者:
Lin MH;Pope BD 3rd;Sasaki T;Keeley DP;Sherwood DR;Miner JH

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半壳素(Hemicentins,HMCNs)是一类细胞外基质蛋白家族,最早发现于C. elegans,在脊椎动物中有两个直系同源物(HMCN 1和2)。在蠕虫中,HMCN沉积在特定部位,在那里它形成长而细的轨道,通过连接相邻的基底膜(BM)连接两个组织。通过产生CRISPR/Cas9介导的Hmcn 1和Hmcn 2敲除小鼠,我们测试了HMCNs在哺乳动物中执行类似功能的假设。Hmcn 1 −/−小鼠存活且具有生育能力。使用新的敲除小鼠验证的HMCN 1抗体,在野生型小鼠中检测到HMCN 1,其为沿着毛发和胡须毛囊的BM、眼睛巩膜和一些淋巴导管的管腔中的精细轨迹。在肾小球的系膜基质中也观察到。然而,HMCN 1缺乏并不影响这些组织的功能,包括毛和胡须的粘附,淋巴导管的筛选功能,或对注射抗原的免疫反应。HMCN 2缺陷本身或与HMCN 1缺陷结合时不会导致任何可辨别的表型。Hmcn 1 −/−、Hmcn 2 −/−和Hmcn 1/2双基因敲除小鼠没有表现出任何明显的表型,这意味着fibulin家族的其他成员进行了补偿。
Hemicentins (HMCNs) are a family of extracellular matrix proteins first identified in C. elegans, with two orthologs (HMCN1 and 2) in vertebrates. In worms, HMCN is deposited at specific sites where it forms long, fine tracks that link two tissues by connecting adjacent basement membranes (BMs). By generating CRISPR/Cas9-mediated Hmcn1 and Hmcn2 knockout mice, we tested the hypothesis that HMCNs perform similar functions in mammals. Hmcn1−/− mice were viable and fertile. Using new, knockout mouse-validated HMCN1 antibodies, HMCN1 was detected in wild-type mice as fine tracks along the BM of hair and whisker follicles, in the sclera of the eyes, and in the lumen of some lymphoid conduits. It was also observed in the mesangial matrix of the kidney glomerulus. However, HMCN1 deficiency did not affect the functions of these tissues, including adherence of coat hairs and whiskers, the sieving function of lymphoid conduits, or the immune response to injected antigens. HMCN2 deficiency did not lead to any discernible phenotypes on its own or when combined with HMCN1 deficiency. That Hmcn1−/−, Hmcn2−/−, and Hmcn1/2 double knockout mice did not display any overt phenotypes implicates compensation by other members of the fibulin family.
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