@article{1c59727005fc4fb2a980d72e57bbbf12,
title = "Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues",
abstract = "Background: Hemicentins (HMCNs) are a family of extracellular matrix proteins first identified in Caenorhabditis 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. Results: 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. Conclusion: That Hmcn1−/−, Hmcn2−/−, and Hmcn1/2 double knockout mice did not display any overt phenotypes implicates compensation by other members of the fibulin family.",
keywords = "basement membrane, hair follicle, lymphoid conduits, matrix protein, sclera, whisker follicle",
author = "Lin, {Meei Hua} and Pope, {Bill D.} and Takako Sasaki and Keeley, {Daniel P.} and Sherwood, {David R.} and Miner, {Jeffrey H.}",
note = "Funding Information: We thank Renate Lewis of the Transgenic Vectors Core for design and validation of the guide RNAs, the Mouse Genetics Core for generating the knockout mice and for mouse husbandry and urine collections, and Jennifer Richardson for genotyping the mice. We also thank Brian Kim for providing the human skin biopsy sample, Yoav Segal for providing mutant mice, and Alexander Nystrom, Gwendalyn Randolph, Rafa Sanguinetti Czepielewski, and Emma Erlich for helpful discussions. This work was funded by NIH grants R01DK078314 to JHM and R35GM118049 to DRS. Col4a5 Funding Information: We thank Renate Lewis of the Transgenic Vectors Core for design and validation of the guide RNAs, the Mouse Genetics Core for generating the knockout mice and for mouse husbandry and urine collections, and Jennifer Richardson for genotyping the mice. We also thank Brian Kim for providing the human skin biopsy sample, Yoav Segal for providing Col4a5 mutant mice, and Alexander Nystrom, Gwendalyn Randolph, Rafa Sanguinetti Czepielewski, and Emma Erlich for helpful discussions. This work was funded by NIH grants R01DK078314 to JHM and R35GM118049 to DRS. Publisher Copyright: {\textcopyright} 2020 Wiley Periodicals, Inc.",
year = "2020",
month = jun,
day = "1",
doi = "10.1002/dvdy.159",
language = "English",
volume = "249",
pages = "775--788",
journal = "Developmental Dynamics",
issn = "1058-8388",
number = "6",
}