Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+3pN1
Donating Investigator Paul Bornstein, University of Washington
Mice homozygous for this targeted mutation are viable and fertile. Multiple analyses has confirmed the absence of protein in embryonic and adult tissue of homozygous mice. Homozygotes exhibit skin disorders (abnormal collagen fiber patterns, reduced tensile strength, increased fragility) and skin fibroblasts have attachment defects. Mice also exhibit an increase in total density/cortical thickness of the long bones, abnormally long bleeding times, and a significant increase in blood vessel density. Homozygous mice exhibit accelerated wound healing after biopsy and accelerated/increased tumor formation following chemically-induced skin carcinogenesis. Mutant mice may be useful in studies of collagen fibrillogenesis in skin and tendons, angiogenesis and vascular pathophysiology, wound healing, chemically-induced tumor progression, and as a potential model for Ehlers Danlos syndrome.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description as published results become available.
A targeting vector was designed to replace exon 2, containing the translation start site, and exon 3 of the endogenous gene with a phosphoglycerate kinase?neomycin resistance cassette (PGK-neo) cassette. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric males were bred with C57BL/6J females. Heterozygous offspring were bred to create a homozygous colony.
|Considerations for Choosing Controls|
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.Intervertebral Disc Disease; IDD (THBS2)
View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.
Thbs2tm1Bst/Thbs2tm1Bsteither: (involves: 129S4/SvJae * 129X1/SvJ) or (involves: 129X1/SvJ)
- premature death
- behavior/neurological phenotype
- abnormal tail movements
- little control of tail movement (MGI Ref ID J:45509)
- tail dragging
- when moving (MGI Ref ID J:45509)
- cardiovascular system phenotype
- abnormal blood vessel morphology
- increased density of small and medium blood vessels in many tissues (MGI Ref ID J:45509)
- abnormal angiogenesis
- increased number and size of blood vessels associated with tumor vascularization (MGI Ref ID J:69756)
- bleeding diathesis (tendency to bleed) (MGI Ref ID J:45509)
- hematopoietic system phenotype
- increased platelet cell number (MGI Ref ID J:45509)
- limbs/digits/tail phenotype
- abnormal tail morphology
- muscle phenotype
- abnormal tendon morphology
- skeleton phenotype
- abnormal ligament morphology
- lax (MGI Ref ID J:45509)
- abnormal tendon morphology
- increased bone mineral density (MGI Ref ID J:45509)
- increased compact bone thickness (MGI Ref ID J:45509)
- homeostasis/metabolism phenotype
- enhanced wound healing
- more rapid healing than control animals after excisional (biopsy punch) wounds (MGI Ref ID J:58476)
- increased bleeding time
- prolonged bleeding time (MGI Ref ID J:45509)
- increased incidence of tumors by chemical induction
- integument phenotype
- abnormal cutaneous collagen fibril morphology
- decreased skin tensile strength
- skin very fragile (MGI Ref ID J:45509)
- cellular phenotype
- decreased apoptosis
- decreased tumor cell apoptosis (MGI Ref ID J:69756)
- increased incidence of tumors by chemical inductionView Research ApplicationsResearch ApplicationsThis mouse can be used to support research in many areas including:
Increased Tumor Incidence
Skin Cancers: Induced
Skin and Hair Texture Defects
Developmental Biology Research
Skin and Hair Texture Defects
|Allele Name||targeted mutation 1, Paul Bornstein|
|Allele Type||Targeted (Null/Knockout)|
|Common Name(s)||TSP2-; Thbs2-; Tsp-2-;|
|Mutation Made By||Paul Bornstein, University of Washington|
|Strain of Origin||129|
|ES Cell Line Name||Other (see notes)|
|ES Cell Line Strain||129|
|Gene Symbol and Name||Thbs2, thrombospondin 2|
|Gene Common Name(s)||TSP-2; TSP2; Thbs-2; Thrombospondin-2;|
|General Note||ES cell line = J1 (129S4/SvJae) or R1 ((129X1/SvJ x 129S1/Sv)F1-Kitl+).|
|Molecular Note||A neomycin resistance cassette replaced a 2.6kb genomic fragment containing exons 2 and 3. Northern blot analysis demonstrated that no transcript was produced from this allele and Western blot analysis revealed that the protein was not detectable in homozygous E17 embryos. [MGI Ref ID J:45509]|
Agah A; Kyriakides TR; Bornstein P. 2005. Proteolysis of cell-surface tissue transglutaminase by matrix metalloproteinase-2 contributes to the adhesive defect and matrix abnormalities in thrombospondin-2-null fibroblasts and mice. Am J Pathol 167(1):81-8. [PubMed: 15972954] [MGI Ref ID J:99511]
Agah A; Kyriakides TR; Lawler J; Bornstein P. 2002. The lack of thrombospondin-1 (TSP1) dictates the course of wound healing in double-TSP1/TSP2-null mice. Am J Pathol 161(3):831-9. [PubMed: 12213711] [MGI Ref ID J:78876]
Agah A; Kyriakides TR; Letrondo N; Bjorkblom B; Bornstein P. 2004. Thrombospondin 2 levels are increased in aged mice: consequences for cutaneous wound healing and angiogenesis. Matrix Biol 22(7):539-47. [PubMed: 14996433] [MGI Ref ID J:98113]
Allamand V; Donahue KM; Straub V; Davisson RL; Davidson BL; Campbell KP. 2000. Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice. Gene Ther 7(16):1385-91. [PubMed: 10981665] [MGI Ref ID J:196642]
Bornstein P; Kyriakides TR; Yang Z; Armstrong LC; Birk DE. 2000. Thrombospondin 2 modulates collagen fibrillogenesis and angiogenesis. J Investig Dermatol Symp Proc 5(1):61-6. [PubMed: 11147677] [MGI Ref ID J:66573]
Chatterjee A; Oh DJ; Kang MH; Rhee DJ. 2013. Central corneal thickness does not correlate with TonoLab-measured IOP in several mouse strains with single transgenic mutations of matricellular proteins. Exp Eye Res 115:106-12. [PubMed: 23806329] [MGI Ref ID J:210410]
Cursiefen C; Masli S; Ng TF; Dana MR; Bornstein P; Lawler J; Streilein JW. 2004. Roles of thrombospondin-1 and -2 in regulating corneal and iris angiogenesis. Invest Ophthalmol Vis Sci 45(4):1117-24. [PubMed: 15037577] [MGI Ref ID J:90088]
Eroglu C; Allen NJ; Susman MW; O'Rourke NA; Park CY; Ozkan E; Chakraborty C; Mulinyawe SB; Annis DS; Huberman AD; Green EM; Lawler J; Dolmetsch R; Garcia KC; Smith SJ; Luo ZD; Rosenthal A; Mosher DF; Barres BA. 2009. Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell 139(2):380-92. [PubMed: 19818485] [MGI Ref ID J:157311]
Fears CY; Grammer JR; Stewart JE Jr; Annis DS; Mosher DF; Bornstein P; Gladson CL. 2005. Low-density lipoprotein receptor-related protein contributes to the antiangiogenic activity of thrombospondin-2 in a murine glioma model. Cancer Res 65(20):9338-46. [PubMed: 16230396] [MGI Ref ID J:102397]
Haddadin RI; Oh DJ; Kang MH; Villarreal G Jr; Kang JH; Jin R; Gong H; Rhee DJ. 2012. Thrombospondin-1 (TSP1)-null and TSP2-null mice exhibit lower intraocular pressures. Invest Ophthalmol Vis Sci 53(10):6708-17. [PubMed: 22930728] [MGI Ref ID J:214057]
Hankenson KD; Ausk BJ; Bain SD; Bornstein P; Gross TS; Srinivasan S. 2006. Mice lacking thrombospondin 2 show an atypical pattern of endocortical and periosteal bone formation in response to mechanical loading. Bone 38(3):310-6. [PubMed: 16290255] [MGI Ref ID J:107885]
Hankenson KD; Bain SD; Kyriakides TR; Smith EA; Goldstein SA; Bornstein P. 2000. Increased marrow-derived osteoprogenitor cells and endosteal bone formation in mice lacking thrombospondin 2. J Bone Miner Res 15(5):851-62. [PubMed: 10804014] [MGI Ref ID J:111972]
Hankenson KD; James IE; Apone S; Stroup GB; Blake SM; Liang X; Lark MW; Bornstein P. 2005. Increased osteoblastogenesis and decreased bone resorption protect against ovariectomy-induced bone loss in thrombospondin-2-null mice. Matrix Biol 24(5):362-70. [PubMed: 15979292] [MGI Ref ID J:100150]
Hawighorst T; Velasco P; Streit M; Hong YK; Kyriakides TR; Brown LF; Bornstein P; Detmar M. 2001. Thrombospondin-2 plays a protective role in multistep carcinogenesis: a novel host anti-tumor defense mechanism. EMBO J 20(11):2631-40. [PubMed: 11387198] [MGI Ref ID J:69756]
Isenberg JS; Annis DS; Pendrak ML; Ptaszynska M; Frazier WA; Mosher DF; Roberts DD. 2009. Differential interactions of thrombospondin-1, -2, and -4 with CD47 and effects on cGMP signaling and ischemic injury responses. J Biol Chem 284(2):1116-25. [PubMed: 19004835] [MGI Ref ID J:145567]
Isenberg JS; Maxhimer JB; Hyodo F; Pendrak ML; Ridnour LA; DeGraff WG; Tsokos M; Wink DA; Roberts DD. 2008. Thrombospondin-1 and CD47 limit cell and tissue survival of radiation injury. Am J Pathol 173(4):1100-12. [PubMed: 18787106] [MGI Ref ID J:139652]
Klocke J; Barcia RN; Heimer S; Cario E; Zieske J; Gilmore MS; Ksander BR; Gregory MS. 2011. Spontaneous bacterial keratitis in CD36 knockout mice. Invest Ophthalmol Vis Sci 52(1):256-63. [PubMed: 20847111] [MGI Ref ID J:171560]
Kokenyesi R; Armstrong LC; Agah A; Artal R; Bornstein P. 2004. Thrombospondin 2 deficiency in pregnant mice results in premature softening of the uterine cervix. Biol Reprod 70(2):385-90. [PubMed: 14561659] [MGI Ref ID J:96727]
Kopp HG; Hooper AT; Broekman MJ; Avecilla ST; Petit I; Luo M; Milde T; Ramos CA; Zhang F; Kopp T; Bornstein P; Jin DK; Marcus AJ; Rafii S. 2006. Thrombospondins deployed by thrombopoietic cells determine angiogenic switch and extent of revascularization. J Clin Invest 116(12):3277-91. [PubMed: 17143334] [MGI Ref ID J:117351]
Krady MM; Zeng J; Yu J; MacLauchlan S; Skokos EA; Tian W; Bornstein P; Sessa WC; Kyriakides TR. 2008. Thrombospondin-2 modulates extracellular matrix remodeling during physiological angiogenesis. Am J Pathol 173(3):879-91. [PubMed: 18688033] [MGI Ref ID J:139584]
Kyriakides TR; Leach KJ; Hoffman AS; Ratner BD; Bornstein P. 1999. Mice that lack the angiogenesis inhibitor, thrombospondin 2, mount an altered foreign body reaction characterized by increased vascularity. Proc Natl Acad Sci U S A 96(8):4449-54. [PubMed: 10200282] [MGI Ref ID J:54581]
Kyriakides TR; Rojnuckarin P; Reidy MA; Hankenson KD; Papayannopoulou T; Kaushansky K; Bornstein P. 2003. Megakaryocytes require thrombospondin-2 for normal platelet formation and function. Blood 101(10):3915-23. [PubMed: 12732502] [MGI Ref ID J:83450]
Kyriakides TR; Zhu YH; Smith LT; Bain SD; Yang Z; Lin MT; Danielson KG; Iozzo RV; LaMarca M; McKinney CE; Ginns EI; 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. J Cell Biol 140(2):419-30. [PubMed: 9442117] [MGI Ref ID J:45509]
Kyriakides TR; Zhu YH; Yang Z; Bornstein P. 1998. The distribution of the matricellular protein thrombospondin 2 in tissues of embryonic and adult mice. J Histochem Cytochem 46(9):1007-15. [PubMed: 9705966] [MGI Ref ID J:49437]
Kyriakides TR; Zhu YH; Yang Z; Huynh G; Bornstein P. 2001. Altered extracellular matrix remodeling and angiogenesis in sponge granulomas of thrombospondin 2-null mice. Am J Pathol 159(4):1255-62. [PubMed: 11583953] [MGI Ref ID J:71943]
Lamy L; Foussat A; Brown EJ; Bornstein P; Ticchioni M; Bernard A. 2007. Interactions between CD47 and thrombospondin reduce inflammation. J Immunol 178(9):5930-9. [PubMed: 17442977] [MGI Ref ID J:145825]
Lange-Asschenfeldt B; Weninger W; Velasco P; Kyriakides TR; von Andrian UH; Bornstein P; Detmar M. 2002. Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2--deficient mice. Blood 99(2):538-45. [PubMed: 11781236] [MGI Ref ID J:109754]
MacLauchlan S; Yu J; Parrish M; Asoulin TA; Schleicher M; Krady MM; Zeng J; Huang PL; Sessa WC; Kyriakides TR. 2011. Endothelial nitric oxide synthase controls the expression of the angiogenesis inhibitor thrombospondin 2. Proc Natl Acad Sci U S A 108(46):E1137-45. [PubMed: 21949402] [MGI Ref ID J:180003]
Maclauchlan S; Skokos EA; Agah A; Zeng J; Tian W; Davidson JM; Bornstein P; Kyriakides TR. 2009. Enhanced angiogenesis and reduced contraction in thrombospondin-2-null wounds is associated with increased levels of matrix metalloproteinases-2 and -9, and soluble VEGF. J Histochem Cytochem 57(4):301-13. [PubMed: 19029404] [MGI Ref ID J:154157]
Nishiwaki T; Yamaguchi T; Zhao C; Amano H; Hankenson KD; Bornstein P; Toyama Y; Matsuo K. 2006. Reduced expression of thrombospondins and craniofacial dysmorphism in mice overexpressing Fra1. J Bone Miner Res 21(4):596-604. [PubMed: 16598380] [MGI Ref ID J:128117]
Puolakkainen PA; Bradshaw AD; Brekken RA; Reed MJ; Kyriakides T; Funk SE; Gooden MD; Vernon RB; Wight TN; Bornstein P; Sage EH. 2005. SPARC-thrombospondin-2-double-null mice exhibit enhanced cutaneous wound healing and increased fibrovascular invasion of subcutaneous polyvinyl alcohol sponges. J Histochem Cytochem 53(5):571-81. [PubMed: 15872050] [MGI Ref ID J:105538]
Schroen B; Heymans S; Sharma U; Blankesteijn WM; Pokharel S; Cleutjens JP; Porter JG; Evelo CT; Duisters R; van Leeuwen RE; Janssen BJ; Debets JJ; Smits JF; Daemen MJ; Crijns HJ; Bornstein P; Pinto YM. 2004. Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Circ Res 95(5):515-22. [PubMed: 15284191] [MGI Ref ID J:101487]
Swinnen M; Vanhoutte D; Van Almen GC; Hamdani N; Schellings MW; D'hooge J; Van der Velden J; Weaver MS; Sage EH; Bornstein P; Verheyen FK; VandenDriessche T; Chuah MK; Westermann D; Paulus WJ; Van de Werf F; Schroen B; Carmeliet P; Pinto YM; Heymans S. 2009. Absence of thrombospondin-2 causes age-related dilated cardiomyopathy. Circulation 120(16):1585-97. [PubMed: 19805649] [MGI Ref ID J:167495]
Taylor DK; Meganck JA; Terkhorn S; Rajani R; Naik A; O'Keefe RJ; Goldstein SA; Hankenson KD. 2009. Thrombospondin-2 influences the proportion of cartilage and bone during fracture healing. J Bone Miner Res 24(6):1043-54. [PubMed: 19123916] [MGI Ref ID J:168670]
Tian W; Sawyer A; Kocaoglu FB; Kyriakides TR. 2011. Astrocyte-derived thrombospondin-2 is critical for the repair of the blood-brain barrier. Am J Pathol 179(2):860-8. [PubMed: 21704005] [MGI Ref ID J:174407]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry When maintaining a live colony, these mice can be bred as homozygotes.
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
|Pricing for International shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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