Expression in SPARC-null mice of collagen type I lacking the globular domain of the α1(I) N-propeptide results in abdominal hernias and loss of dermal collagen
| Autor: | Lauren Card, Amy D. Bradshaw, Nikki Henderson, Paul Bornstein, Yuhua Zhang |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Phosphopeptides
Mice 129 Strain Transgene Mice Transgenic Article Collagen Type I Extracellular matrix Mice Exon Hydroxyproline chemistry.chemical_compound Dermis medicine Animals Osteonectin Mortality Molecular Biology Mice Knockout biology Chemistry Exons Molecular biology Extracellular Matrix Hernia Abdominal Protein Structure Tertiary Collagen Type I alpha 1 Chain Mice Inbred C57BL Collagen type I alpha 1 Procollagen peptidase Phenotype medicine.anatomical_structure biology.protein Collagen Gene Deletion Procollagen |
| Zdroj: | Matrix Biology. 29:559-564 |
| ISSN: | 0945-053X |
| DOI: | 10.1016/j.matbio.2010.08.002 |
| Popis: | The sequence encoding the N-propeptide of collagen I is characterized by significant conservation of amino acids across species; however, the function of the N-propeptide remains poorly defined. Studies in vitro have suggested that one activity of this propeptide might be to act as a feedback inhibitor of collagen I synthesis. To determine whether the N-propeptide contributed to decreased collagen content in SPARC-null mice, mice carrying a deletion of exon 2, which encodes the globular domain of the N-propeptide of collagen I, were crossed to SPARC-null animals. Mice lacking SPARC and expressing collagen I without the globular domain of the N-propeptide were viable and fertile. However, a significant number of animals developed abdominal hernias within the first 2 months of life with an approximate 20% penetrance (~35% of males). The dermis of SPARC-null/exon 2-deleted mice was thinner and contained fewer large collagen fibers in comparison with wild-type or in either single transgenic animal. The average collagen fibril diameter of exon 2-deleted mice did not significantly differ from wild-type mice (WT: 87.9 nm versus exon 2-deleted: 88.2 nm), whereas SPARC-null/exon 2-deleted fibrils were smaller than that of SPARC-null dermis (SPARC-null: 60.2 nm, SPARC-null/exon 2-deleted: 40.8 nm). As measured by hydroxyproline analysis, double transgenic skin biopsies contained significantly less collagen than those of wild-type, those of exon 2-deleted, and those of SPARC-null biopsies. Acetic acid extraction of collagen from skin biopsies revealed an increase in the proportion of soluble collagen in the SPARC-null/exon 2-deleted mice. These results support a function of the N-propeptide of collagen I in facilitating incorporation and stabilization of collagen I into the insoluble ECM and argue against a primary function of the N-propeptide as a negative regulator of collagen synthesis. |
| Databáze: | OpenAIRE |
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