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Updated: Dec 29, 2025

Analysis of Protein-protein Interactions and Co-localization Between Components of Gap, Tight, and Adherens Junctions in Murine Mammary Glands
Published on: May 30, 2017
Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues
Meei-Hua Lin1, Bill D Pope1, Takako Sasaki2
1Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Insights
Hemicentins (HMCNs) are extracellular matrix proteins. Studies in knockout mice show that HMCN1 and HMCN2 do not appear essential for mammalian tissue function, suggesting compensatory mechanisms.
Area of Science:
- Extracellular Matrix Biology
- Developmental Biology
- Genetics
Background:
- Hemicentins (HMCNs) are extracellular matrix proteins found in C. elegans, forming tracks that link tissues.
- Vertebrates possess two HMCN orthologs, HMCN1 and HMCN2.
- The function of HMCNs in mammals remained largely unexplored.
Purpose of the Study:
- To investigate the in vivo function of Hemicentins (HMCN1 and HMCN2) in mammals.
- To determine if HMCNs play a role in tissue structure and function in mice.
Main Methods:
- Generation of CRISPR/Cas9-mediated Hmcn1 and Hmcn2 knockout mice.
- Utilized newly developed, validated HMCN1 antibodies for detection in wild-type mice.
- Phenotypic analysis of single and double knockout mice.
Main Results:
- Hmcn1 knockout mice were viable and fertile with no apparent functional deficits.
- HMCN1 was localized to basement membranes of hair follicles, sclera, lymphoid conduits, and kidney glomeruli.
- Absence of HMCN1 or HMCN2 did not impact hair adherence, lymphoid conduit function, or immune responses.
Conclusions:
- Hmcn1 and Hmcn2 knockout mice exhibit no overt phenotypes, indicating a lack of essential function in these specific contexts.
- The absence of phenotypes suggests potential functional redundancy or compensation by other extracellular matrix proteins, possibly fibulins.
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.
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