| A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. | |
| | |
| Jump to Full Text | |
MedLine Citation:
|
PMID: 7790374 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Degradation of type I collagen, the most abundant collagen, is initiated by collagenase cleavage at a highly conserved site between Gly775 and Ile776 of the alpha 1 (I) chain. Mutations at or around this site render type I collagen resistant to collagenase digestion in vitro. We show here that mice carrying a collagenase-resistant mutant Col1a-1 transgene die late in embryo-genesis, ascribable to overexpression of the transgene, since the same mutation introduced into the endogenous Col1a-1 gene by gene targeting permitted normal development of mutant mice to young adulthood. With increasing age, animals carrying the targeted mutation developed marked fibrosis of the dermis similar to that in human scleroderma. Postpartum involution of the uterus in the mutant mice was also impaired, with persistence of collagenous nodules in the uterine wall. Although type I collagen from the homozygous mutant mice was resistant to cleavage by human or rat fibroblast collagenases at the helical site, only the rat collagenase cleaved collagen trimers at an additional, novel site in the nonhelical N-telopeptide domain. Our results suggest that cleavage by murine collagenase at the N-telopeptide site could account for resorption of type I collagen during embryonic and early adult life. During intense collagen resorption, however, such as in the immediate postpartum uterus and in the dermis later in life, cleavage at the helical site is essential for normal collagen turnover. Thus, type I collagen is degraded by at least two differentially controlled mechanisms involving collagenases with distinct, but overlapping, substrate specificities. |
| | |
Authors:
|
X Liu; H Wu; M Byrne; J Jeffrey; S Krane; R Jaenisch |
Related Documents
:
|
7774024 - Disaccharides as endomannosidase inhibitors: syntheses of alpha-homomannojirimycin and ... 7573384 - Relationships between mesangial cell proliferation and types i and iv collagen mrna lev... 3815404 - The structure of the antigenic lipopolysaccharide o-chains produced by salmonella urban... 3197834 - Sulfated n-linked carbohydrate chains in porcine thyroglobulin. 7247474 - A metabolic dysfunction in early murine osteoarthritis. 17270084 - Biocompatibility of polypyrrole particles: an in-vivo study in mice. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: The Journal of cell biology Volume: 130 ISSN: 0021-9525 ISO Abbreviation: J. Cell Biol. Publication Date: 1995 Jul |
Date Detail:
|
Created Date: 1995-07-27 Completed Date: 1995-07-27 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 0375356 Medline TA: J Cell Biol Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 227-37 Citation Subset: IM |
Affiliation:
|
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Collagen / physiology* Collagenases / metabolism* Female Genes, Lethal Male Mice Mice, Transgenic Molecular Sequence Data Mutagenesis, Site-Directed Protein Processing, Post-Translational Skin Diseases / genetics, pathology Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
|
AR03564/AR/NIAMS NIH HHS; AR07258/AR/NIAMS NIH HHS; HD05291/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
|
9007-34-5/Collagen; EC 3.4.24.-/Collagenases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
| Full Text | |
|
Journal Information Journal ID (nlm-ta): J Cell Biol ISSN: 0021-9525 ISSN: 1540-8140 Publisher: The Rockefeller University Press |
Article Information Download PDF  Print publication date: Day: 1 Month: 7 Year: 1995 Volume: 130 Issue: 1 First Page: 227 Last Page: 237 ID: 2120510 Publisher Id: 95310362 PubMed Id: 7790374 |
| A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling | |
Article Categories:
|
|
Previous Document: Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects.
Next Document: Functional characterization of the 180-kD ribosome receptor in vivo.