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Gene Review

Thbs2  -  thrombospondin 2

Mus musculus

Synonyms: TSP2, Thbs-2, Thrombospondin-2, Tsp2
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Disease relevance of Thbs2


High impact information on Thbs2

  • While TSP-2 deficiency did not affect tumor differentiation or proliferation, tumor cell apoptosis was significantly reduced [5].
  • These results reveal upregulation of an endogenous angiogenesis inhibitor during multi step tumorigenesis and identify enhanced stromal TSP-2 expression as a novel host anti-tumor defense mechanism [5].
  • Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis [6].
  • 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 [6].
  • 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 [6].

Chemical compound and disease context of Thbs2


Biological context of Thbs2

  • Thbs2 is located on chromosome 17, band A3, whereas Thbs1 was found on chromosome 2, band F [9].
  • The exon/intron organization of Thbs2 is highly conserved in comparison with Thbs1 in that exon size and the pattern of interruption of the reading frame by introns are preserved, but there is a marked divergence in coding sequence, primarily in the first 7 exons [9].
  • Interestingly, TSP1 and TSP2 exhibited markedly different tissue- and stage-specific patterns of mRNA expression during mouse embryogenesis, implying that the two TSP molecules possess discrete functional properties important for development [10].
  • Characterization of mouse thrombospondin 2 sequence and expression during cell growth and development [10].
  • Based on their translated amino acid sequences, it seems likely that TSP1 and TSP2 will be found to have both common and unique properties and that the functional consequences of TSP production will reflect the ratio of the levels of these two related proteins [11].

Anatomical context of Thbs2


Associations of Thbs2 with chemical compounds

  • In addition, homotrimeric TSP2 has a lower affinity for heparin than homotrimeric TSP1 [13].
  • Degradation of TSP2 was slower in cultures of Chinese hamster ovary (CHO) cells lacking heparan sulfate proteoglycans than in wild type CHO cells or in cultures of 3T3 cells treated with heparitinase than in untreated 3T3 cells [14].
  • In addition, the NH2-terminal domain of TSP3 differs markedly, both in sequence and in exon/intron structure, from that in TSP1 or TSP2 [15].
  • After a 4-week implantation period, both types of PDMS elicited a similar FBR with a collagenous capsule in both TSP2-null and control mice [16].
  • Consistent with this hypothesis, MKs take up recombinant TSP2 in an integrin-dependent manner when it is supplied in the culture medium [17].

Physical interactions of Thbs2


Other interactions of Thbs2

  • To define the molecular requirements for assembly of fascin spikes by thrombospondins, we developed a panel of recombinant protein units of TSP-1 and TSP-2; these were designed according to the domain boundaries and included matched monomeric and trimeric units [19].
  • Using the corneal pocket assay we found that TSP-2 did not inhibit bFGF-induced angiogenesis in CD36 null mice [20].
  • PSC were isolated by outgrowth from normal mouse pancreas and expression of TSP-1 and TSP-2 was evaluated after serum-activation [21].
  • Consistent with this finding, there was a decrease in expression of collagen and osteocalcin RNA by TSP2-null MSCs on day 7 and increased osteopontin expression on day 7 and day 14 [22].
  • More recently, TSP1, TSP2, and SPARC have also been implicated in the foreign body response, an unusual reaction to injury that occurs after the implantation of biomaterials [23].

Analytical, diagnostic and therapeutic context of Thbs2

  • We compared the distributions of TSP1 and TSP2 in mouse embryos (day 10 and later) by immunohistochemistry [2].
  • Western blotting showed that TSP2 was expressed in the cervix of mice on Days 14 and 18 of pregnancy but not on Day 10 or in the nonpregnant animal [24].
  • Thus, TSP2-null mice provide an animal model to assist in the understanding of the molecular basis of spontaneous, premature softening of the uterine cervix [24].
  • Morphologically, the TSP2-null and wild-type (WT) cell populations were similar and by flow cytometry contained equivalent numbers of CD44+, Mac1+, intercellular adhesion molecule-1 (ICAM-1+), and ScaI+ cells [22].
  • Determination of TSP2 protein content by Western analysis and RNA levels by reverse-transcription polymerase chain reaction (RT-PCR) indicated that MSCs are the primary source of TSP2 in the marrow and secrete abundant TSP2 into culture medium [22].


  1. Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing fra1. Nishiwaki, T., Yamaguchi, T., Zhao, C., Amano, H., Kurt, D.H., Bornstein, P., Toyama, Y., Matsuo, K. J. Bone Miner. Res. (2006) [Pubmed]
  2. Restricted localization of thrombospondin-2 protein during mouse embryogenesis: a comparison to thrombospondin-1. Tooney, P.A., Sakai, T., Sakai, K., Aeschlimann, D., Mosher, D.F. Matrix Biol. (1998) [Pubmed]
  3. Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice. Kyriakides, T.R., Zhu, Y.H., Yang, Z., Huynh, G., Bornstein, P. Am. J. Pathol. (2001) [Pubmed]
  4. Roles of thrombospondin-1 and -2 in regulating corneal and iris angiogenesis. Cursiefen, C., Masli, S., Ng, T.F., Dana, M.R., Bornstein, P., Lawler, J., Streilein, J.W. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  5. Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism. Hawighorst, T., Velasco, P., Streit, M., Hong, Y.K., Kyriakides, T.R., Brown, L.F., Bornstein, P., Detmar, M. EMBO J. (2001) [Pubmed]
  6. Mice that lack thrombospondin 2 display connective tissue abnormalities that are associated with disordered collagen fibrillogenesis, an increased vascular density, and a bleeding diathesis. 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. J. Cell Biol. (1998) [Pubmed]
  7. Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Schroen, B., Heymans, S., Sharma, U., Blankesteijn, W.M., Pokharel, S., Cleutjens, J.P., Porter, J.G., Evelo, C.T., Duisters, R., van Leeuwen, R.E., Janssen, B.J., Debets, J.J., Smits, J.F., Daemen, M.J., Crijns, H.J., Bornstein, P., Pinto, Y.M. Circ. Res. (2004) [Pubmed]
  8. Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2--deficient mice. Lange-Asschenfeldt, B., Weninger, W., Velasco, P., Kyriakides, T.R., von Andrian, U.H., Bornstein, P., Detmar, M. Blood (2002) [Pubmed]
  9. A second thrombospondin gene in the mouse is similar in organization to thrombospondin 1 but does not respond to serum. Bornstein, P., Devarayalu, S., Li, P., Disteche, C.M., Framson, P. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  10. Characterization of mouse thrombospondin 2 sequence and expression during cell growth and development. Laherty, C.D., O'Rourke, K., Wolf, F.W., Katz, R., Seldin, M.F., Dixit, V.M. J. Biol. Chem. (1992) [Pubmed]
  11. A second, expressed thrombospondin gene (Thbs2) exists in the mouse genome. Bornstein, P., O'Rourke, K., Wikstrom, K., Wolf, F.W., Katz, R., Li, P., Dixit, V.M. J. Biol. Chem. (1991) [Pubmed]
  12. Differential expression of thrombospondin 1, 2, and 3 during murine development. Iruela-Arispe, M.L., Liska, D.J., Sage, E.H., Bornstein, P. Dev. Dyn. (1993) [Pubmed]
  13. Thrombospondin 1 and thrombospondin 2 are expressed as both homo- and heterotrimers. O'Rourke, K.M., Laherty, C.D., Dixit, V.M. J. Biol. Chem. (1992) [Pubmed]
  14. Metabolism of thrombospondin 2. Binding and degradation by 3t3 cells and glycosaminoglycan-variant Chinese hamster ovary cells. Chen, H., Strickland, D.K., Mosher, D.F. J. Biol. Chem. (1996) [Pubmed]
  15. Isolation and characterization of the mouse thrombospondin 3 (Thbs3) gene. Bornstein, P., Devarayalu, S., Edelhoff, S., Disteche, C.M. Genomics (1993) [Pubmed]
  16. Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity. Kyriakides, T.R., Leach, K.J., Hoffman, A.S., Ratner, B.D., Bornstein, P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  17. Megakaryocytes require thrombospondin-2 for normal platelet formation and function. Kyriakides, T.R., Rojnuckarin, P., Reidy, M.A., Hankenson, K.D., Papayannopoulou, T., Kaushansky, K., Bornstein, P. Blood (2003) [Pubmed]
  18. Thrombospondin 2 potentiates notch3/jagged1 signaling. Meng, H., Zhang, X., Hankenson, K.D., Wang, M.M. J. Biol. Chem. (2009) [Pubmed]
  19. Trimeric assembly of the C-terminal region of thrombospondin-1 or thrombospondin-2 is necessary for cell spreading and fascin spike organisation. Anilkumar, N., Annis, D.S., Mosher, D.F., Adams, J.C. J. Cell. Sci. (2002) [Pubmed]
  20. The antiangiogenic effect of thrombospondin-2 is mediated by CD36 and modulated by histidine-rich glycoprotein. Simantov, R., Febbraio, M., Silverstein, R.L. Matrix Biol. (2005) [Pubmed]
  21. Induced thrombospondin expression in the mouse pancreas during pancreatic injury. Neuschwander-Tetri, B.A., Talkad, V., Otis Stephen, F. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  22. The secreted protein thrombospondin 2 is an autocrine inhibitor of marrow stromal cell proliferation. Hankenson, K.D., Bornstein, P. J. Bone Miner. Res. (2002) [Pubmed]
  23. Matricellular proteins as modulators of wound healing and the foreign body response. Kyriakides, T.R., Bornstein, P. Thromb. Haemost. (2003) [Pubmed]
  24. Thrombospondin 2 deficiency in pregnant mice results in premature softening of the uterine cervix. Kokenyesi, R., Armstrong, L.C., Agah, A., Artal, R., Bornstein, P. Biol. Reprod. (2004) [Pubmed]
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