Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

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. Species laboratory mouse Generation N10pN1 Generation Definitions   Donating Investigator David Ginsburg,   University of Michigan

Description
Mice homozygous for this targeted mutation are viable and fertile. On the C57BL/6 background, the mice have a mild procoagulant phenotype using the ferric chloride vascular injury model, and von Willebrand factor (VWF)-mediated platelet interactions are slightly prolonged compared to wildtype (using intravital microscopy). There is no sponataneous thrombotic thrombocytopenic purpura (TTP) phenotype. Expression of the targeted exons has been eliminated in the liver, as tested by RT-PCR. There is no detectable activity of the enzyme in the plasma of homozygous targeted mice.

Development
A targeting vector was designed to replace exons 1-6 with a PGK/Neomycin cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. Targeted clones were injected into C57BL/6J blastocysts. The strain was backcrossed twelve times to C57BL/6 by the donating laboratory.

Related Strains

Strains carrying other alleles of Adamts13

007236

B6.129X1(FVB)-Adamts13tm2Dgi/J

View Strains carrying other alleles of Adamts13     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Thrombotic Thrombocytopenic Purpura, Congenital; TTP

- No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Thrombotic Thrombocytopenic Purpura, Congenital; TTP

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Adamts13^tm1Dgi/Adamts13^tm1Dgi

        B6.129X1-Adamts13^tm1Dgi

• homeostasis/metabolism phenotype
• abnormal blood coagulation
  • following FeCl3 injury, mice exhibit a reduced time to clot formation and vessel occlusion compared with similarly treated wild-type mice   (MGI Ref ID J:133469)

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

Adamts13^tm1Dgi/Adamts13^tm1Dgi

        involves: 129X1/SvJ * C57BL/6J

• normal phenotype
• no abnormal phenotype detected
  • exhibit normal development, fertility, survival, blood smears and a similar response to shiga toxin as wildtype, even though von Willebrand Factor (vWF)-cleaving activity is lost, unlike on a background that contains CASA/Rk   (MGI Ref ID J:101752)

Adamts13^tm1Dgi/Adamts13^tm1Dgi

        involves: 129X1/SvJ * C57BL/6J * CASA/Rk

• mortality/aging
• *normal* mortality/aging
  • associated phenotypes appear after crossing to CASA/Rk mice   (MGI Ref ID J:101752)
• • premature death
    • exhibit a significant decrease in survival than wildtype   (MGI Ref ID J:101752)
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype
  • associated phenotypes appear after crossing to CASA/Rk mice   (MGI Ref ID J:101752)
• • abnormal erythrocyte morphology
    • peripheral blood smear shows schistocytes and fragmented red blood cells   (MGI Ref ID J:101752)
  • abnormal platelet physiology
    • platelets show significantly prolonged adhesion to endothelial cells   (MGI Ref ID J:101752)
  • decreased platelet cell number
    • decrease in average platelet count in peripheral blood   (MGI Ref ID J:101752)
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • associated phenotypes appear after crossing to CASA/Rk mice   (MGI Ref ID J:101752)
• • abnormal circulating protein level
    • 40-50% increase in mean plasma von Willebrand Factor (vWF) level   (MGI Ref ID J:101752)
    • appearance of ultra-long vWF similar to the pattern observed in human thrombotic thrombocytopenic purpura (TPP)   (MGI Ref ID J:101752)
  • abnormal platelet physiology
    • platelets show significantly prolonged adhesion to endothelial cells   (MGI Ref ID J:101752)
  • thrombosis
    • exhibit widespread vWF-rich and fibrin-poor hyaline thrombi in the small vessels of multiple organs   (MGI Ref ID J:101752)
• immune system phenotype
• *normal* immune system phenotype
  • associated phenotypes appear after crossing to CASA/Rk mice   (MGI Ref ID J:101752)
• • increased susceptibility to bacterial infection
    • shiga toxin injection causes increased mortality, thrombocytopenia, microangiopathic hemolytic anemia and widespread vWF-rich and fibrin-poor hyaline thrombi in the small vessels of multiple organs and results in a syndrome closely resembling human thrombotic thrombocytopenic purpura   (MGI Ref ID J:101752)

View Research Applications

Research Applications

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

Hematological Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Adamts13tm1Dgi
Allele Name		targeted mutation 1, David Ginsburg
Allele Type		Targeted (knock-out)
Common Name(s)		Adamts13-;
Mutation Made By		David Ginsburg,   University of Michigan
Strain of Origin		129X1/SvJ
ES Cell Line Strain		129
Gene Symbol and Name		Adamts13, a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 13
Chromosome		2
Gene Common Name(s)		13; ADAM-TS; ADAM-TS13; ADAMTS-13; C9orf8; Gm710; LOC279028; TTP; VWFCP; vWF-CP; vWF-CP mRNA for von Willebrand factor-cleaving;
Molecular Note		A neomycin resistance gene replaced exons 1-6. RT-PCR of mutant liver samples confirmed absence of transcript. [MGI Ref ID J:101752]

Genotyping

Genotyping Information

Genotyping Protocols

Adamts13^tm1Dgi, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Motto DG; Chauhan AK; Zhu G; Homeister J; Lamb CB; Desch KC; Zhang W; Tsai HM; Wagner DD; Ginsburg D. 2005. Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice. J Clin Invest 115(10):2752-61. [PubMed: 16200209]  [MGI Ref ID J:101752]

Additional References

Adamts13^tm1Dgi related

Chauhan AK; Kisucka J; Brill A; Walsh MT; Scheiflinger F; Wagner DD. 2008. ADAMTS13: a new link between thrombosis and inflammation. J Exp Med 205(9):2065-74. [PubMed: 18695007]  [MGI Ref ID J:142125]

Chauhan AK; Motto DG; Lamb CB; Bergmeier W; Dockal M; Plaimauer B; Scheiflinger F; Ginsburg D; Wagner DD. 2006. Systemic antithrombotic effects of ADAMTS13. J Exp Med 203(3):767-76. [PubMed: 16533881]  [MGI Ref ID J:123759]

Chauhan AK; Walsh MT; Zhu G; Ginsburg D; Wagner DD; Motto DG. 2008. The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis. Blood 111(7):3452-7. [PubMed: 18083848]  [MGI Ref ID J:133469]

Chen J; Reheman A; Gushiken FC; Nolasco L; Fu X; Moake JL; Ni H; Lopez JA. 2011. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest 121(2):593-603. [PubMed: 21266777]  [MGI Ref ID J:171826]

De Meyer SF; Savchenko AS; Haas MS; Schatzberg D; Carroll MC; Schiviz A; Dietrich B; Rottensteiner H; Scheiflinger F; Wagner DD. 2012. Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice. Blood 120(26):5217-23. [PubMed: 22915644]  [MGI Ref ID J:192140]

Gandhi C; Khan MM; Lentz SR; Chauhan AK. 2012. ADAMTS13 reduces vascular inflammation and the development of early atherosclerosis in mice. Blood 119(10):2385-91. [PubMed: 22123843]  [MGI Ref ID J:182469]

Gandhi C; Motto DG; Jensen M; Lentz SR; Chauhan AK. 2012. ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice. Blood 120(26):5224-30. [PubMed: 22983446]  [MGI Ref ID J:192128]

Huang J; Motto DG; Bundle DR; Sadler JE. 2010. Shiga toxin B subunits induce VWF secretion by human endothelial cells and thrombotic microangiopathy in ADAMTS13-deficient mice. Blood 116(18):3653-9. [PubMed: 20644116]  [MGI Ref ID J:166480]

Laje P; Shang D; Cao W; Niiya M; Endo M; Radu A; DeRogatis N; Scheiflinger F; Zoltick PW; Flake AW; Zheng XL. 2009. Correction of murine ADAMTS13 deficiency by hematopoietic progenitor cell-mediated gene therapy. Blood 113(10):2172-80. [PubMed: 19141866]  [MGI Ref ID J:146165]

Petruzziello-Pellegrini TN; Yuen DA; Page AV; Patel S; Soltyk AM; Matouk CC; Wong DK; Turgeon PJ; Fish JE; Ho JJ; Steer BM; Khajoee V; Tigdi J; Lee WL; Motto DG; Advani A; Gilbert RE; Karumanchi SA; Robinson LA; Tarr PI; Liles WC; Brunton JL; Marsden PA. 2012. The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice. J Clin Invest 122(2):759-76. [PubMed: 22232208]  [MGI Ref ID J:184379]

Raife TJ; Cao W; Atkinson BS; Bedell B; Montgomery RR; Lentz SR; Johnson GF; Zheng XL. 2009. Leukocyte proteases cleave von Willebrand factor at or near the ADAMTS13 cleavage site. Blood 114(8):1666-74. [PubMed: 19541819]  [MGI Ref ID J:152263]

Rayes J; Hollestelle MJ; Legendre P; Marx I; de Groot PG; Christophe OD; Lenting PJ; Denis CV. 2010. Mutation and ADAMTS13-dependent modulation of disease severity in a mouse model for von Willebrand disease type 2B. Blood 115(23):4870-7. [PubMed: 20200350]  [MGI Ref ID J:161564]

Schiviz A; Wuersch K; Piskernik C; Dietrich B; Hoellriegl W; Rottensteiner H; Scheiflinger F; Schwarz HP; Muchitsch EM. 2012. A new mouse model mimicking thrombotic thrombocytopenic purpura: correction of symptoms by recombinant human ADAMTS13. Blood 119(25):6128-35. [PubMed: 22529289]  [MGI Ref ID J:188653]

Tati R; Kristoffersson AC; Stahl AL; Morgelin M; Motto D; Satchell S; Mathieson P; Manea-Hedstrom M; Karpman D. 2011. Phenotypic Expression of ADAMTS13 in Glomerular Endothelial Cells. PLoS One 6(6):e21587. [PubMed: 21720563]  [MGI Ref ID J:174381]

Zhao BQ; Chauhan AK; Canault M; Patten IS; Yang JJ; Dockal M; Scheiflinger F; Wagner DD. 2009. von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke. Blood 114(15):3329-34. [PubMed: 19687510]  [MGI Ref ID J:153541]

Health & husbandry

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Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

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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.

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