DOI: 10.1083/jcb.140.2.419. Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis

Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis

10.1083/jcb.140.2.419

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Thrombospondin (TSP) 2, and its close relative TSP1, are extracellular proteins whose functions are complex, poorly understood, and controversial. In an attempt to determine the function of TSP2, we disrupted the Thbs2 gene by homologous recombination in embryonic stem cells, and generated TSP2-null mice by blastocyst injection and appropriate breeding of mutant animals. Thbs2−/− mice were produced with the expected Mendelian frequency, appeared overtly normal, and were fertile. However, on closer examination, these mice displayed a wide variety of abnormalities. Collagen fiber patterns in skin were disordered, and abnormally large fibrils with irregular contours were observed by electron microscopy in both skin and tendon. As a functional correlate of these findings, the skin was fragile and had reduced tensile strength, and the tail was unusually flexible. Mutant skin fibroblasts were defective in attachment to a substratum. An increase in total density and in cortical thickness of long bones was documented by histology and quantitative computer tomography. Mutant mice also manifested an abnormal bleeding time, and histologic surveys of mouse tissues, stained with an antibody to von Willebrand factor, showed a significant increase in blood vessels. The basis for the unusual phenotype of the TSP2-null mouse could derive from the structural role that TSP2 might play in collagen fibrillogenesis in skin and tendon. However, it seems likely that some of the diverse manifestations of this genetic disorder result from the ability of TSP2 to modulate the cell surface properties of mesenchymal cells, and thus, to affect cell functions such as adhesion and migration.

Bibliography

Kyriakides, T. R., Zhu, Y.-H., Smith, L. T., Bain, S. D., Yang, Z., Lin, M. T., Danielson, K. G., Iozzo, R. V., LaMarca, M., McKinney, C. E., Ginns, E. I., & Bornstein, P. (1998). Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis. The Journal of Cell Biology, 140(2), 419â430.

Authors 12

Themis R. Kyriakides (first)
Yu-Hong Zhu (additional)
Lynne T. Smith (additional)
Steven D. Bain (additional)
Zhantao Yang (additional)
Ming T. Lin (additional)
Keith G. Danielson (additional)
Renato V. Iozzo (additional)
Mary LaMarca (additional)
Cindy E. McKinney (additional)
Edward I. Ginns (additional)
Paul Bornstein (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:46 p.m.)
Deposited	2 years, 1 month ago (July 28, 2023, 6:44 p.m.)
Indexed	4 days, 15 hours ago (Aug. 26, 2025, 2:30 a.m.)
Issued	27 years, 7 months ago (Jan. 26, 1998)
Published	27 years, 7 months ago (Jan. 26, 1998)
Published Online	27 years, 7 months ago (Jan. 26, 1998)
Published Print	27 years, 7 months ago (Jan. 26, 1998)

Funders 0

None

BibTeX

@article{Kyriakides_1998, title={Mice That Lack Thrombospondin 2 Display Connective Tissue Abnormalities That Are Associated with Disordered Collagen Fibrillogenesis, an Increased Vascular Density, and a Bleeding Diathesis}, volume={140}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.140.2.419}, DOI={10.1083/jcb.140.2.419}, number={2}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Kyriakides, Themis R. and Zhu, Yu-Hong and Smith, Lynne T. and Bain, Steven D. and Yang, Zhantao and Lin, Ming T. and Danielson, Keith G. and Iozzo, Renato V. and LaMarca, Mary and McKinney, Cindy E. and Ginns, Edward I. and Bornstein, Paul}, year={1998}, month=jan, pages={419–430} }

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