Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote         (Female x Male)   10-OCT-06 Species laboratory mouse Generation N8+F13 (17-FEB-11) Generation Definitions   Donating Investigator Jack Lawler,   Beth Israel Deaconess Medical Center

Description
Mice homozygous for this targeted mutation are viable and fertile, with an approximate 20% decrease in embryo/neonate viability and a mild and variable lordotic curvature of the spine apparent from birth. Homozygous mice have an abnormal, but no full length transcript in multiple tissues. Western analysis confirmed the absence of the protein in platelets. Homozygotes exhibit an increase in the number of circulating white blood cells. During the first four to ten weeks of life, homozygotes exhibit patches of acute and organizing pneumonia. At later time points, there is considerable hyperplasia of the various epithelial cell lineages. Mutant mice also have an increased number of retinal endothelial cells and inappropriate remodeling and maturation of retinal vasculature following injury. On the FVB/N background, spontaneous tumor growth and vasculature are significantly increased compared to wildtype. Mutant mice may be useful in studies of inflammatory responses in the lungs, eye, and skin, angiogenesis and vascular pathophysiology, cancer, chemotherapy, apoptosis, and cell differentiation and migration.

Development
A targeting vector was designed to replace exon 2, intron 3, and exon 3 of the endogenous gene with a phosphoglycerate kinase–neomycin resistance cassette (PGK-neo) cassette. This construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric males were bred with C57BL/6J females. Mutant mice were backcrossed to C57BL/6J for 8 generations prior to sending to The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Sjogren Syndrome

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Thbs1^tm1Hyn/Thbs1^tm1Hyn

        either: (involves: 129S2/SvPas * 129/Sv) or (involves: 129S2/SvPas * C57BL/6)

• mortality/aging
• partial prenatal lethality
  • fewer than expected number of homozygous mutant mice born after heterozygous matings   (MGI Ref ID J:46182)
  • incomplete penetrance   (MGI Ref ID J:46182)
• cardiovascular system phenotype
• abnormal heart ventricle morphology   (MGI Ref ID J:48446)
• • abnormal interventricular septum morphology
    • enlarged myocytes within ventricular septum   (MGI Ref ID J:48446)
• abnormal lung vasculature morphology
  • bronchiolar arteries thickened, tortuous, with smooth muscle cell hyperplasia   (MGI Ref ID J:48446)
• pulmonary alveolar hemorrhage
  • hemorrhage into the alveoli   (MGI Ref ID J:48446)
• vascular smooth muscle cell hyperplasia   (MGI Ref ID J:48446)
• digestive/alimentary phenotype
• esophagogastric junction metaplasia   (MGI Ref ID J:48446)
• exocrine pancreas hypoplasia   (MGI Ref ID J:48446)
• stomach epithelial hyperplasia   (MGI Ref ID J:48446)
• endocrine/exocrine gland phenotype
• abnormal cystic duct morphology
  • dilation of ducts adjacent to distended gall bladder   (MGI Ref ID J:48446)
• abnormal pancreas morphology
  • increased vascularity   (MGI Ref ID J:48446)
• • exocrine pancreas hypoplasia   (MGI Ref ID J:48446)
  • pancreatic islet hyperplasia   (MGI Ref ID J:48446)
• dilated gallbladder
  • distended gall bladder   (MGI Ref ID J:48446)
• pancreas inflammation   (MGI Ref ID J:48446)
• hematopoietic system phenotype
• increased leukocyte cell number   (MGI Ref ID J:46182)
• • increased eosinophil cell number
    • increased differential percentage   (MGI Ref ID J:46182)
  • increased lymphocyte cell number   (MGI Ref ID J:46182)
  • increased monocyte cell number
    • increased differential percentage   (MGI Ref ID J:46182)
  • increased neutrophil cell number   (MGI Ref ID J:46182)
• immune system phenotype
• increased leukocyte cell number   (MGI Ref ID J:46182)
• • increased eosinophil cell number
    • increased differential percentage   (MGI Ref ID J:46182)
  • increased lymphocyte cell number   (MGI Ref ID J:46182)
  • increased monocyte cell number
    • increased differential percentage   (MGI Ref ID J:46182)
  • increased neutrophil cell number   (MGI Ref ID J:46182)
• lung inflammation   (MGI Ref ID J:48446)
  • pneumonia arose between 1 and 4 months of life   (MGI Ref ID J:46182)
• pancreas inflammation   (MGI Ref ID J:48446)
• liver/biliary system phenotype
• abnormal cystic duct morphology
  • dilation of ducts adjacent to distended gall bladder   (MGI Ref ID J:48446)
• dilated gallbladder
  • distended gall bladder   (MGI Ref ID J:48446)
• muscle phenotype
• vascular smooth muscle cell hyperplasia   (MGI Ref ID J:48446)
• renal/urinary system phenotype
• abnormal kidney corticomedullary boundary morphology
  • indistinct cortico-medullary junction   (MGI Ref ID J:48446)
• reproductive system phenotype
• decreased litter size   (MGI Ref ID J:46182)
• reduced fertility
  • homozygous matings produced significantly fewer cumulative litters per breeding pair than wild-type matings   (MGI Ref ID J:46182)
• respiratory system phenotype
• abnormal lung morphology
  • proximal mucinous metaplasia   (MGI Ref ID J:48446)
• • abnormal lung vasculature morphology
    • bronchiolar arteries thickened, tortuous, with smooth muscle cell hyperplasia   (MGI Ref ID J:48446)
  • bronchial epithelial hyperplasia   (MGI Ref ID J:48446)
  • increased Clara cell number   (MGI Ref ID J:48446)
• lung inflammation   (MGI Ref ID J:48446)
  • pneumonia arose between 1 and 4 months of life   (MGI Ref ID J:46182)
• pulmonary alveolar hemorrhage
  • hemorrhage into the alveoli   (MGI Ref ID J:48446)
• skeleton phenotype
• kyphosis   (MGI Ref ID J:48446)
• lordosis
  • apparent from birth   (MGI Ref ID J:46182)
• integument phenotype
• abnormal dermal layer morphology
  • lack of dermal matrix   (MGI Ref ID J:48446)
  • increased dermal vascular density   (MGI Ref ID J:48446)

Thbs1^tm1Hyn/Thbs1^tm1Hyn

        involves: 129S2/SvPas * C57BL/6

• vision/eye phenotype
• abnormal conjunctiva morphology
  • younger mice exhibit an increase in numbers goblet cells in the conjunctiva while in older mice they are decreased compared to in wild-type mice   (MGI Ref ID J:153126)
  • age-related decline in conjunctiva goblet cell density is worse than in wild-type mice   (MGI Ref ID J:153126)
• abnormal cornea morphology
  • older mice exhibit corneal edema unlike wild-type mice   (MGI Ref ID J:153126)
• • abnormal corneal epithelium morphology
    • mice exhibit damage in the corneal epithelial barrier unlike wild-type mice   (MGI Ref ID J:153126)
• abnormal lacrimal gland physiology
  • stimulated lacrimal function is abolished compared to in similarly treated wild-type lacrimal gland fragments   (MGI Ref ID J:153126)
  • tear peroxidase declines in older mice   (MGI Ref ID J:153126)
  • lacrimal function is lost as early as 8 weeks   (MGI Ref ID J:153126)
  • lacrimal gland tissue produces more IL17 than in wild-type mice   (MGI Ref ID J:153126)
  • apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice   (MGI Ref ID J:153126)
  • mice exhibit deterioration in the lacrimal gland unlike wild-type mice   (MGI Ref ID J:153126)
• • lacrimal gland inflammation
    • at 24 and 48 weeks, mononuclear infiltrates are increased compared to in wild-type mice   (MGI Ref ID J:153126)
    • mice exhibit an increase in CD4+ T cells compared with wild-type mice   (MGI Ref ID J:153126)
• microphthalmia
  • mice exhibit a progressive reduction in eye size characterized by eye closure and eventual loss of the eye   (MGI Ref ID J:153126)
• narrow eye opening
  • mice develop dry crusty eyes that eventually close   (MGI Ref ID J:153126)
• immune system phenotype
• decreased interferon-gamma secretion
  • in splenocytes of older mice   (MGI Ref ID J:153126)
• decreased regulatory T cell number
  • the number of Foxp3+ regulatory T cells in the spleen is decreased compared to in wild-type mice   (MGI Ref ID J:153126)
• increased CD4-positive T cell number
  • in the lacrimal glands   (MGI Ref ID J:153126)
• increased anti-single stranded DNA antibody level
  • at 8 weeks, mice exhibit an increase in serum anti-SSA and anti-SSB autoantibodies compared with wild-type mice   (MGI Ref ID J:153126)
• increased interleukin-17 secretion
  • at 8 to 12 weeks, mice exhibit a 2-fold increase in IL17+ splenocytes compared with wild-type mice   (MGI Ref ID J:153126)
  • lacrimal gland tissue produces more IL17 than in wild-type mice   (MGI Ref ID J:153126)
  • in older mice, IL17 secretion from splenocytes is increased compared to in wild-type mice   (MGI Ref ID J:153126)
• lacrimal gland inflammation
  • at 24 and 48 weeks, mononuclear infiltrates are increased compared to in wild-type mice   (MGI Ref ID J:153126)
  • mice exhibit an increase in CD4+ T cells compared with wild-type mice   (MGI Ref ID J:153126)
• hematopoietic system phenotype
• decreased regulatory T cell number
  • the number of Foxp3+ regulatory T cells in the spleen is decreased compared to in wild-type mice   (MGI Ref ID J:153126)
• increased CD4-positive T cell number
  • in the lacrimal glands   (MGI Ref ID J:153126)
• endocrine/exocrine gland phenotype
• abnormal lacrimal gland physiology
  • stimulated lacrimal function is abolished compared to in similarly treated wild-type lacrimal gland fragments   (MGI Ref ID J:153126)
  • tear peroxidase declines in older mice   (MGI Ref ID J:153126)
  • lacrimal function is lost as early as 8 weeks   (MGI Ref ID J:153126)
  • lacrimal gland tissue produces more IL17 than in wild-type mice   (MGI Ref ID J:153126)
  • apoptosis in the lacrimal gland of young mice is increased compared to in wild-type mice   (MGI Ref ID J:153126)
  • mice exhibit deterioration in the lacrimal gland unlike wild-type mice   (MGI Ref ID J:153126)
• • lacrimal gland inflammation
    • at 24 and 48 weeks, mononuclear infiltrates are increased compared to in wild-type mice   (MGI Ref ID J:153126)
    • mice exhibit an increase in CD4+ T cells compared with wild-type mice   (MGI Ref ID J:153126)
• cardiovascular system phenotype
• abnormal systemic arterial blood pressure
  • DEA/NO treatment causes a greater hypotensive effect than in controls   (MGI Ref ID J:148948)
• • decreased pulse pressure
    • significantly decreased relative to controls   (MGI Ref ID J:148948)
  • increased mean systemic arterial blood pressure
    • dark cycle mean arterial pressure is significantly increased relative to controls   (MGI Ref ID J:148948)
  • increased systemic arterial diastolic blood pressure
    • dark cycle diastolic pressure is increased relative to controls   (MGI Ref ID J:148948)
• decreased heart rate   (MGI Ref ID J:148948)
• integument phenotype
• decreased sensitivity to skin irradiation
  • hair is preserved after 25 Gy irradiation   (MGI Ref ID J:139652)
  • minimal or no skin ulceration 8 weeks after irradiation   (MGI Ref ID J:139652)
  • hair follicles and skin architecture are better preserved than in controls   (MGI Ref ID J:139652)
• muscle phenotype
• *normal* muscle phenotype
  • no leg muscle atrophy after irradiation   (MGI Ref ID J:139652)
  • limb flexibility maintained   (MGI Ref ID J:139652)
• • abnormal muscle fiber morphology
    • less loss of muscle fibers and nuclei after irradiation   (MGI Ref ID J:139652)
• cellular phenotype
• *normal* cellular phenotype
  • mitochondrial viability and function is preserved after irradiation   (MGI Ref ID J:139652)

Thbs1^tm1Hyn/Thbs1^tm1Hyn

        involves: 129S2/SvPas

• integument phenotype
• *normal* integument phenotype
  • normal cutaneous architecture is maintained in myocutaneous skin flap preparations   (MGI Ref ID J:133700)
• • abnormal skin physiology
    • improved myocutaneous skin flap survival 7 days after the surgery as compared to controls   (MGI Ref ID J:133700)
    • reduced necrosis   (MGI Ref ID J:133700)
• limbs/digits/tail phenotype
• abnormal hindlimb morphology
  • better tissue survival after proximal ligation of the external iliac and common femoral   (MGI Ref ID J:133700)
  • minimal or no clinical evidence of tissue necrosis   (MGI Ref ID J:133700)
  • increased vascular remodeling and vascular perfusion by 1 week after the operation   (MGI Ref ID J:133700)
• cardiovascular system phenotype
• abnormal physiological neovascularization
  • increased vascular remodeling and vascular perfusion by 1 week after proximal ligation of the external iliac and common femoral   (MGI Ref ID J:133700)
• cellular phenotype
• abnormal mitochondrial physiology   (MGI Ref ID J:133700)
• decreased renal tubule apoptosis
  • at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit a significant reduction in the number of TUNEL-positive tubules in kidney cortices compared with similarly treated wild-type mice   (MGI Ref ID J:104708)
• homeostasis/metabolism phenotype
• decreased susceptibility to kidney reperfusion injury
  • at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit significantly lower serum creatinine levels and show significantly less tubular dilatation, cast formation, loss of brush border, focal epithelial vacuolization and necrosis in the cortex than similarly treated wild-type mice   (MGI Ref ID J:104708)
• renal/urinary system phenotype
• decreased renal tubule apoptosis
  • at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit a significant reduction in the number of TUNEL-positive tubules in kidney cortices compared with similarly treated wild-type mice   (MGI Ref ID J:104708)
• decreased susceptibility to kidney reperfusion injury
  • at 24-hr of kidney ischemia/reperfusion (IR) injury, mice exhibit significantly lower serum creatinine levels and show significantly less tubular dilatation, cast formation, loss of brush border, focal epithelial vacuolization and necrosis in the cortex than similarly treated wild-type mice   (MGI Ref ID J:104708)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Apoptosis Research
Endogenous Regulators
Extracellular Modulators

Cancer Research
Genes Regulating Growth and Proliferation

Cardiovascular Research
Ischemia studies
Vascular Defects

Cell Biology Research
Defects in Extracellular Matrix Molecules

Developmental Biology Research
Embryonic Lethality (Homozygous)
      incomplete

Internal/Organ Research
Lung Defects
Lymphoid Tissue Defects
Wound Healing

Research Tools
Apoptosis Research
Cancer Research
Cardiovascular Research
Hematological Research
Immunology and Inflammation Research
Internal/Organ Research
Sensorineural Research

Sensorineural Research
Eye Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Thbs1tm1Hyn
Allele Name		targeted mutation 1, Richard Hynes
Allele Type		Targeted (knock-out)
Common Name(s)		TSP-1; TSP-1-; TSP1-; Thbs1-; Tsp-1KO; tbsp1-;
Mutation Made By		Jack Lawler,   Beth Israel Deaconess Medical Center
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Thbs1, thrombospondin 1
Chromosome		2
Gene Common Name(s)		THBS; THBS-1; TSP; TSP-1; TSP1; Thbs-1; tbsp1;
Molecular Note		A neomycin selection cassette replaced exon 2, intron 3, and exon 3. An RNase protection assay demonstrated that no detectable transcript was present in multiple tissues of homozygous animals. Western analysis confirmed the absence of the encoded protein. [MGI Ref ID J:46182]

Genotyping

Genotyping Information

Genotyping Protocols

Thbs1^tm1Hyn, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lawler J; Sunday M; Thibert V; Duquette M; George EL; Rayburn H ; Hynes RO. 1998. Thrombospondin-1 is required for normal murine pulmonary homeostasis and its absence causes pneumonia. J Clin Invest 101(5):982-92. [PubMed: 9486968]  [MGI Ref ID J:46182]

Additional References

Thbs1^tm1Hyn related

Abdelouahed M; Ludlow A; Brunner G; Lawler J. 2000. Activation of platelet-transforming growth factor beta-1 in the absence of thrombospondin-1. J Biol Chem 275(24):17933-6. [PubMed: 10849431]  [MGI Ref ID J:62821]

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]

Ahamed J; Janczak CA; Wittkowski KM; Coller BS. 2009. In vitro and in vivo evidence that thrombospondin-1 (TSP-1) contributes to stirring- and shear-dependent activation of platelet-derived TGF-beta1. PLoS One 4(8):e6608. [PubMed: 19672301]  [MGI Ref ID J:152471]

Ali NA; Gaughan AA; Orosz CG; Baran CP; McMaken S; Wang Y; Eubank TD; Hunter M; Lichtenberger FJ; Flavahan NA; Lawler J; Marsh CB. 2008. Latency associated peptide has in vitro and in vivo immune effects independent of TGF-beta1. PLoS ONE 3(4):e1914. [PubMed: 18392110]  [MGI Ref ID J:134350]

Bauer EM; Qin Y; Miller TW; Bandle RW; Csanyi G; Pagano PJ; Bauer PM; Schnermann J; Roberts DD; Isenberg JS. 2010. Thrombospondin-1 supports blood pressure by limiting eNOS activation and endothelial-dependent vasorelaxation. Cardiovasc Res 88(3):471-81. [PubMed: 20610415]  [MGI Ref ID J:183150]

Blake SM; Strasser V; Andrade N; Duit S; Hofbauer R; Schneider WJ; Nimpf J. 2008. Thrombospondin-1 binds to ApoER2 and VLDL receptor and functions in postnatal neuronal migration. EMBO J 27(22):3069-80. [PubMed: 18946489]  [MGI Ref ID J:143787]

Bonnefoy A; Daenens K; Feys HB; De Vos R; Vandervoort P; Vermylen J; Lawler J; Hoylaerts MF. 2006. Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13. Blood 107(3):955-64. [PubMed: 16204318]  [MGI Ref ID J:127571]

Brechot N; Gomez E; Bignon M; Khallou-Laschet J; Dussiot M; Cazes A; Alanio-Brechot C; Durand M; Philippe J; Silvestre JS; Van Rooijen N; Corvol P; Nicoletti A; Chazaud B; Germain S. 2008. Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice. PLoS ONE 3(12):e3950. [PubMed: 19079608]  [MGI Ref ID J:144359]

Budhani F; Leonard KA; Bergdahl A; Gao J; Lawler J; Davis EC. 2007. Vascular response to intra-arterial injury in the thrombospondin-1 null mouse. J Mol Cell Cardiol 43(2):210-4. [PubMed: 17583726]  [MGI Ref ID J:123075]

Chen M; Copland DA; Zhao J; Liu J; Forrester JV; Dick AD; Xu H. 2012. Persistent inflammation subverts thrombospondin-1-induced regulation of retinal angiogenesis and is driven by CCR2 ligation. Am J Pathol 180(1):235-45. [PubMed: 22067906]  [MGI Ref ID J:180169]

Crawford SE; Stellmach V; Murphy-Ullrich JE; Ribeiro SM; Lawler J; Hynes RO; Boivin GP; Bouck N. 1998. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell 93(7):1159-70. [PubMed: 9657149]  [MGI Ref ID J:48446]

Cursiefen C; Maruyama K; Bock F; Saban D; Sadrai Z; Lawler J; Dana R; Masli S. 2011. Thrombospondin 1 inhibits inflammatory lymphangiogenesis by CD36 ligation on monocytes. J Exp Med 208(5):1083-92. [PubMed: 21536744]  [MGI Ref ID J:177296]

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]

Daniel C; Schaub K; Amann K; Lawler J; Hugo C. 2007. Thrombospondin-1 is an endogenous activator of TGF-beta in experimental diabetic nephropathy in vivo. Diabetes 56(12):2982-9. [PubMed: 17878288]  [MGI Ref ID J:132311]

Diamond AG; Gonterman RM; Anderson AL; Menon K; Offutt CD; Weaver CH; Philbrick WM; Foley J. 2006. Parathyroid Hormone Hormone-Related Protein and the PTH Receptor Regulate Angiogenesis of the Skin. J Invest Dermatol 126(9):2127-34. [PubMed: 16675960]  [MGI Ref ID J:111733]

Drott CJ; Olerud J; Emanuelsson H; Christoffersson G; Carlsson PO. 2012. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice. PLoS One 7(10):e47451. [PubMed: 23094049]  [MGI Ref ID J:192180]

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]

Evrard S; Bluteau O; Tulliez M; Rameau P; Gonin P; Zetterberg E; Palmblad J; Bonnefoy A; Villeval JL; Vainchenker W; Giraudier S; Wagner-Ballon O. 2011. Thrombospondin-1 is not the major activator of TGF-beta1 in thrombopoietin-induced myelofibrosis. Blood 117(1):246-9. [PubMed: 20944070]  [MGI Ref ID J:168424]

Feng W; Madajka M; Kerr BA; Mahabeleshwar GH; Whiteheart SW; Byzova TV. 2011. A novel role for platelet secretion in angiogenesis: mediating bone marrow-derived cell mobilization and homing. Blood 117(14):3893-902. [PubMed: 21224474]  [MGI Ref ID J:172614]

Fitchev PP; Wcislak SM; Lee C; Bergh A; Brendler CB; Stellmach VM; Crawford SE; Mavroudis CD; Cornwell ML; Doll JA. 2010. Thrombospondin-1 regulates the normal prostate in vivo through angiogenesis and TGF-beta activation. Lab Invest 90(7):1078-90. [PubMed: 20458281]  [MGI Ref ID J:162136]

Frangogiannis NG; Ren G; Dewald O; Zymek P; Haudek S; Koerting A; Winkelmann K; Michael LH; Lawler J; Entman ML. 2005. Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation 111(22):2935-42. [PubMed: 15927970]  [MGI Ref ID J:112253]

Futagami Y; Sugita S; Vega J; Ishida K; Takase H; Maruyama K; Aburatani H; Mochizuki M. 2007. Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells. J Immunol 178(11):6994-7005. [PubMed: 17513749]  [MGI Ref ID J:147839]

Garcia O; Torres M; Helguera P; Coskun P; Busciglio J. 2010. A role for thrombospondin-1 deficits in astrocyte-mediated spine and synaptic pathology in Down's syndrome. PLoS One 5(12):e14200. [PubMed: 21152035]  [MGI Ref ID J:167727]

Gutierrez LS; Suckow M; Lawler J; Ploplis VA; Castellino FJ. 2003. Thrombospondin 1--a regulator of adenoma growth and carcinoma progression in the APC(Min/+) mouse model. Carcinogenesis 24(2):199-207. [PubMed: 12584168]  [MGI Ref ID J:79641]

Isenberg JS; Hyodo F; Matsumoto K; Romeo MJ; Abu-Asab M; Tsokos M; Kuppusamy P; Wink DA; Krishna MC; Roberts DD. 2007. Thrombospondin-1 limits ischemic tissue survival by inhibiting nitric oxide-mediated vascular smooth muscle relaxation. Blood 109(5):1945-52. [PubMed: 17082319]  [MGI Ref ID J:145359]

Isenberg JS; Hyodo F; Pappan LK; Abu-Asab M; Tsokos M; Krishna MC; Frazier WA; Roberts DD. 2007. Blocking thrombospondin-1/CD47 signaling alleviates deleterious effects of aging on tissue responses to ischemia. Arterioscler Thromb Vasc Biol 27(12):2582-8. [PubMed: 17916772]  [MGI Ref ID J:147523]

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]

Isenberg JS; Qin Y; Maxhimer JB; Sipes JM; Despres D; Schnermann J; Frazier WA; Roberts DD. 2009. Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress. Matrix Biol 28(2):110-9. [PubMed: 19284971]  [MGI Ref ID J:148948]

Isenberg JS; Ridnour LA; Perruccio EM; Espey MG; Wink DA; Roberts DD. 2005. Thrombospondin-1 inhibits endothelial cell responses to nitric oxide in a cGMP-dependent manner. Proc Natl Acad Sci U S A 102(37):13141-6. [PubMed: 16150726]  [MGI Ref ID J:101420]

Isenberg JS; Romeo MJ; Abu-Asab M; Tsokos M; Oldenborg A; Pappan L; Wink DA; Frazier WA; Roberts DD. 2007. Increasing survival of ischemic tissue by targeting CD47. Circ Res 100(5):712-20. [PubMed: 17293482]  [MGI Ref ID J:133700]

Isenberg JS; Romeo MJ; Yu C; Yu CK; Nghiem K; Monsale J; Rick ME; Wink DA; Frazier WA; Roberts DD. 2008. Thrombospondin-1 stimulates platelet aggregation by blocking the antithrombotic activity of nitric oxide/cGMP signaling. Blood 111(2):613-23. [PubMed: 17890448]  [MGI Ref ID J:129994]

Keino H; Masli S; Sasaki S; Streilein JW; Stein-Streilein J. 2006. CD8+ T regulatory cells use a novel genetic program that includes CD103 to suppress Th1 immunity in eye-derived tolerance. Invest Ophthalmol Vis Sci 47(4):1533-42. [PubMed: 16565389]  [MGI Ref ID J:108447]

Kermorvant-Duchemin E; Sennlaub F; Sirinyan M; Brault S; Andelfinger G; Kooli A; Germain S; Ong H; d'Orleans-Juste P; Gobeil F; Zhu T; Boisvert C; Hardy P; Jain K; Falck JR; Balazy M; Chemtob S. 2005. Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration. Nat Med 11(12):1339-45. [PubMed: 16311602]  [MGI Ref ID J:104131]

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]

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]

Lawler J; Miao WM; Duquette M; Bouck N; Bronson RT; Hynes RO. 2001. Thrombospondin-1 gene expression affects survival and tumor spectrum of p53-deficient mice. Am J Pathol 159(5):1949-56. [PubMed: 11696456]  [MGI Ref ID J:72391]

Lee NV; Sato M; Annis DS; Loo JA; Wu L; Mosher DF; Iruela-Arispe ML. 2006. ADAMTS1 mediates the release of antiangiogenic polypeptides from TSP1 and 2. EMBO J 25(22):5270-83. [PubMed: 17082774]  [MGI Ref ID J:116155]

Lee YJ; Koch M; Karl D; Torres-Collado AX; Fernando NT; Rothrock C; Kuruppu D; Ryeom S; Iruela-Arispe ML; Yoon SS. 2010. Variable inhibition of thrombospondin 1 against liver and lung metastases through differential activation of metalloproteinase ADAMTS1. Cancer Res 70(3):948-56. [PubMed: 20103648]  [MGI Ref ID J:156857]

Li Y; Tong X; Rumala C; Clemons K; Wang S. 2011. Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model. PLoS One 6(10):e26656. [PubMed: 22039525]  [MGI Ref ID J:178082]

Ludlow A; Yee KO; Lipman R; Bronson R; Weinreb P; Huang X; Sheppard D; Lawler J. 2005. Characterization of integrin beta6 and thrombospondin-1 double-null mice. J Cell Mol Med 9(2):421-37. [PubMed: 15963261]  [MGI Ref ID J:100142]

Martin-Manso G; Navarathna DH; Galli S; Soto-Pantoja DR; Kuznetsova SA; Tsokos M; Roberts DD. 2012. Endogenous thrombospondin-1 regulates leukocyte recruitment and activation and accelerates death from systemic candidiasis. PLoS One 7(11):e48775. [PubMed: 23144964]  [MGI Ref ID J:194950]

Masli S; Turpie B; Streilein JW. 2006. Thrombospondin orchestrates the tolerance-promoting properties of TGF{beta}-treated antigen-presenting cells. Int Immunol 18(5):689-99. [PubMed: 16569680]  [MGI Ref ID J:108549]

McMaken S; Exline MC; Mehta P; Piper M; Wang Y; Fischer SN; Newland CA; Schrader CA; Balser SR; Sarkar A; Baran CP; Marsh CB; Cook CH; Phillips GS; Ali NA. 2011. Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity. PLoS One 6(5):e19654. [PubMed: 21573017]  [MGI Ref ID J:172433]

Moura R; Tjwa M; Vandervoort P; Cludts K; Hoylaerts MF. 2007. Thrombospondin-1 activates medial smooth muscle cells and triggers neointima formation upon mouse carotid artery ligation. Arterioscler Thromb Vasc Biol 27(10):2163-9. [PubMed: 17761938]  [MGI Ref ID J:135005]

Moura R; Tjwa M; Vandervoort P; Van Kerckhoven S; Holvoet P; Hoylaerts MF. 2008. Thrombospondin-1 deficiency accelerates atherosclerotic plaque maturation in ApoE-/- mice. Circ Res 103(10):1181-9. [PubMed: 18818405]  [MGI Ref ID J:155289]

Myers SA; DeVries WH; Andres KR; Gruenthal MJ; Benton RL; Hoying JB; Hagg T; Whittemore SR. 2011. CD47 knockout mice exhibit improved recovery from spinal cord injury. Neurobiol Dis 42(1):21-34. [PubMed: 21168495]  [MGI Ref ID J:170731]

Ng TF; Turpie B; Masli S. 2009. Thrombospondin-1-mediated regulation of microglia activation after retinal injury. Invest Ophthalmol Vis Sci 50(11):5472-8. [PubMed: 19494207]  [MGI Ref ID J:154654]

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]

Olerud J; Johansson M; Lawler J; Welsh N; Carlsson PO. 2008. Improved vascular engraftment and graft function after inhibition of the angiostatic factor thrombospondin-1 in mouse pancreatic islets. Diabetes 57(7):1870-7. [PubMed: 18420490]  [MGI Ref ID J:138228]

Olerud J; Mokhtari D; Johansson M; Christoffersson G; Lawler J; Welsh N; Carlsson PO. 2011. Thrombospondin-1: an islet endothelial cell signal of importance for beta-cell function. Diabetes 60(7):1946-54. [PubMed: 21617177]  [MGI Ref ID J:186751]

Otsuka G; Stempien-Otero A; Frutkin AD; Dichek DA. 2007. Mechanisms of TGF-beta1-induced intimal growth: plasminogen-independent activities of plasminogen activator inhibitor-1 and heterogeneous origin of intimal cells. Circ Res 100(9):1300-7. [PubMed: 17431190]  [MGI Ref ID J:137777]

Pimanda JE; Ganderton T; Maekawa A; Yap CL; Lawler J; Kershaw G; Chesterman CN; Hogg PJ. 2004. Role of thrombospondin-1 in control of von Willebrand factor multimer size in mice. J Biol Chem 279(20):21439-48. [PubMed: 14981081]  [MGI Ref ID J:89829]

Posey KL; Hankenson K; Veerisetty AC; Bornstein P; Lawler J; Hecht JT. 2008. Skeletal abnormalities in mice lacking extracellular matrix proteins, thrombospondin-1, thrombospondin-3, thrombospondin-5, and type IX collagen. Am J Pathol 172(6):1664-74. [PubMed: 18467703]  [MGI Ref ID J:136242]

Rodriguez-Manzaneque JC; Lane TF; Ortega MA; Hynes RO; Lawler J; Iruela-Arispe ML. 2001. Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Proc Natl Acad Sci U S A 98(22):12485-90. [PubMed: 11606713]  [MGI Ref ID J:72297]

Saban DR; Bock F; Chauhan SK; Masli S; Dana R. 2010. Thrombospondin-1 derived from APCs regulates their capacity for allosensitization. J Immunol 185(8):4691-7. [PubMed: 20844200]  [MGI Ref ID J:164736]

Scheef EA; Sorenson CM; Sheibani N. 2009. Attenuation of proliferation and migration of retinal pericytes in the absence of thrombospondin-1. Am J Physiol Cell Physiol 296(4):C724-34. [PubMed: 19193867]  [MGI Ref ID J:149692]

Shaked Y; Bertolini F; Man S; Rogers MS; Cervi D; Foutz T; Rawn K; Voskas D; Dumont DJ; Ben-David Y; Lawler J; Henkin J; Huber J; Hicklin DJ; D'Amato RJ; Kerbel RS. 2005. Genetic heterogeneity of the vasculogenic phenotype parallels angiogenesis; Implications for cellular surrogate marker analysis of antiangiogenesis. Cancer Cell 7(1):101-11. [PubMed: 15652753]  [MGI Ref ID J:96033]

Shibahara K; Ota M; Horiguchi M; Yoshinaga K; Melamed J; Rifkin DB. 2013. Production of gastrointestinal tumors in mice by modulating latent TGF-beta1 activation. Cancer Res 73(1):459-68. [PubMed: 23117884]  [MGI Ref ID J:194125]

Sund M; Hamano Y; Sugimoto H; Sudhakar A; Soubasakos M; Yerramalla U; Benjamin LE; Lawler J; Kieran M; Shah A; Kalluri R. 2005. Function of endogenous inhibitors of angiogenesis as endothelium-specific tumor suppressors. Proc Natl Acad Sci U S A 102(8):2934-9. [PubMed: 15710885]  [MGI Ref ID J:97878]

Thakar CV; Zahedi K; Revelo MP; Wang Z; Burnham CE; Barone S; Bevans S; Lentsch AB; Rabb H; Soleimani M. 2005. Identification of thrombospondin 1 (TSP-1) as a novel mediator of cell injury in kidney ischemia. J Clin Invest 115(12):3451-9. [PubMed: 16294224]  [MGI Ref ID J:104708]

Turpie B; Yoshimura T; Gulati A; Rios JD; Dartt DA; Masli S. 2009. Sjogren's syndrome-like ocular surface disease in thrombospondin-1 deficient mice. Am J Pathol 175(3):1136-47. [PubMed: 19700744]  [MGI Ref ID J:153126]

Velasco P; Huegel R; Brasch J; Schroder JM; Weichenthal M; Stockfleth E; Schwarz T; Lawler J; Detmar M; Lange-Asschenfeldt B. 2009. The angiogenesis inhibitor thrombospondin-1 inhibits acute cutaneous hypersensitivity reactions. J Invest Dermatol 129(8):2022-30. [PubMed: 19194474]  [MGI Ref ID J:152510]

Voros G; Lijnen HR. 2006. Deficiency of thrombospondin-1 in mice does not affect adipose tissue development. J Thromb Haemost 4(1):277-8. [PubMed: 16409488]  [MGI Ref ID J:135770]

Wang S; Wu Z; Sorenson CM; Lawler J; Sheibani N. 2003. Thrombospondin-1-deficient mice exhibit increased vascular density during retinal vascular development and are less sensitive to hyperoxia-mediated vessel obliteration. Dev Dyn 228(4):630-42. [PubMed: 14648840]  [MGI Ref ID J:128776]

Wang Y; Wang S; Sheibani N. 2006. Enhanced proangiogenic signaling in thrombospondin-1-deficient retinal endothelial cells. Microvasc Res 71(3):143-51. [PubMed: 16624339]  [MGI Ref ID J:112781]

Xie L; Duncan MB; Pahler J; Sugimoto H; Martino M; Lively J; Mundel T; Soubasakos M; Rubin K; Takeda T; Inoue M; Lawler J; Hynes RO; Hanahan D; Kalluri R. 2011. Counterbalancing angiogenic regulatory factors control the rate of cancer progression and survival in a stage-specific manner. Proc Natl Acad Sci U S A 108(24):9939-44. [PubMed: 21622854]  [MGI Ref ID J:173322]

Yano K; Brown LF; Lawler J; Miyakawa T; Detmar M. 2003. Thrombospondin-1 plays a critical role in the induction of hair follicle involution and vascular regression during the catagen phase. J Invest Dermatol 120(1):14-9. [PubMed: 12535193]  [MGI Ref ID J:133248]

Yee KO; Connolly CM; Pines M; Lawler J. 2006. Halofuginone inhibits tumor growth in the polyoma middle T antigen mouse via a thrombospondin-1 independent mechanism. Cancer Biol Ther 5(2):218-24. [PubMed: 16418571]  [MGI Ref ID J:110390]

Zamiri P; Masli S; Kitaichi N; Taylor AW; Streilein JW. 2005. Thrombospondin plays a vital role in the immune privilege of the eye. Invest Ophthalmol Vis Sci 46(3):908-19. [PubMed: 15728547]  [MGI Ref ID J:105017]

Zaslavsky A; Baek KH; Lynch RC; Short S; Grillo J; Folkman J; Italiano JE Jr; Ryeom S. 2010. Platelet-derived thrombospondin-1 is a critical negative regulator and potential biomarker of angiogenesis. Blood 115(22):4605-13. [PubMed: 20086246]  [MGI Ref ID J:161573]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes. Of note, homozygous matings result in fewer litters and an approximate 20% decrease in embryo/neonate viability.
Mating System	Homozygote x Homozygote         (Female x Male)   10-OCT-06

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.