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

Former Names B6.129-St3gal4tm1Jxm/J    (Changed: 29-JUN-07 ) 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 ?pN1 Generation Definitions   Donating Investigator Jamey D Marth,   Burnham Inst at Univ Calif Santa Barbara

Description
Mice homozygous for this targeted mutation are viable, fertile, and normal in size. They develop a bleeding disorder associated with an autosomal dominant reduction in plasma von Willebrand factor (VWF) and an autosomal recessive thrombocytopenia. The formation of selectin ligands on circulating neutrophils is also substantially reduced. This mutant mouse strain may be useful in studies of leukocyte trafficking and coagulation disorders.

Development
A targeting vector was used to place a floxed neomycin-thymidine kinase expression cassette in the intron upstream of the exon 5 and a loxP site in the intron downstream of exon 7 (encompassing the large sialyl motif). The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were transfected with a Cre expression plasmid to excise the neo cassette and the floxed exons. Gancyclovir-resistant ES cells were injected into blastocysts. Heterozygotes were crossed to ZP3-Cre transgenic mates to produce the recombined and deleted Type 1 allele in the germline. This strain was backcrossed to C57BL/6 at least eight times by the donating laboratory.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Introduction to Cre-lox technology

Phenotype

Phenotype Information

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.

St3gal4^tm1.1Jxm/St3gal4^tm1.1Jxm

        B6.129-St3gal4^tm1.1Jxm

• hematopoietic system phenotype
• abnormal platelet physiology
  • despite an accumulation of platelets in the liver, platelets fail to normally associate with Kupffer cells   (MGI Ref ID J:136946)
• decreased platelet cell number   (MGI Ref ID J:136946)
• homeostasis/metabolism phenotype
• abnormal platelet physiology
  • despite an accumulation of platelets in the liver, platelets fail to normally associate with Kupffer cells   (MGI Ref ID J:136946)
• increased bleeding time   (MGI Ref ID J:136946)
• immune system phenotype
• abnormal leukocyte tethering or rolling
  • after exteriorization of the cremaster muscle, leukocyte rolling flux fraction (RFF), untreated mutants is significantly higher than in controls   (MGI Ref ID J:117085)
  • injection of P-selectin-blocking antibody into mutants completely abolishes rolling, while rolling is reduced in controls; this suggests that L-selectin-mediated rolling is absent in mutants   (MGI Ref ID J:117085)
  • treatment of mice with P- and E-selectin-blocking antibodies after TNFalpha intrascrotal injection dramatically reduces RFF (to <1%) compared to controls   (MGI Ref ID J:117085)
• abnormal response to infection
  • following infection with S. pneumoniae, mice fail to exhibit normal thrombocytopenia and platelet half-life is not decreased as in similarly treated wild-type mice   (MGI Ref ID J:136946)
• cellular phenotype
• abnormal leukocyte tethering or rolling
  • after exteriorization of the cremaster muscle, leukocyte rolling flux fraction (RFF), untreated mutants is significantly higher than in controls   (MGI Ref ID J:117085)
  • injection of P-selectin-blocking antibody into mutants completely abolishes rolling, while rolling is reduced in controls; this suggests that L-selectin-mediated rolling is absent in mutants   (MGI Ref ID J:117085)
  • treatment of mice with P- and E-selectin-blocking antibodies after TNFalpha intrascrotal injection dramatically reduces RFF (to <1%) compared to controls   (MGI Ref ID J:117085)

St3gal4^tm1.1Jxm/St3gal4^tm1.1Jxm

        involves: 129S1/Sv * 129X1/SvJ

• immune system phenotype
• *normal* immune system phenotype
  • mice exhibit normal leukocytosis and recruitment of monocytes   (MGI Ref ID J:189086)
• • abnormal leukocyte migration
    • impaired lymphocyte homing into lymph nodes and Peyer's patches   (MGI Ref ID J:189086)
  • decreased lymphocyte cell number
    • reduced lymphocytes in the abdominal, celiac, mesenteric and inguinal lymph nodes and Peyer's patch   (MGI Ref ID J:189086)
    • however, the number of lymphocytes in the spleen, thymus and bone marrow is normal   (MGI Ref ID J:189086)
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype
  • mice exhibit normal leukocytosis and recruitment of monocytes   (MGI Ref ID J:189086)
• • decreased lymphocyte cell number
    • reduced lymphocytes in the abdominal, celiac, mesenteric and inguinal lymph nodes and Peyer's patch   (MGI Ref ID J:189086)
    • however, the number of lymphocytes in the spleen, thymus and bone marrow is normal   (MGI Ref ID J:189086)
  • decreased platelet cell number   (MGI Ref ID J:189086)
  • increased mean platelet volume   (MGI Ref ID J:189086)
• cellular phenotype
• abnormal leukocyte migration
  • impaired lymphocyte homing into lymph nodes and Peyer's patches   (MGI Ref ID J:189086)

View Research Applications

Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		St3gal4tm1.1Jxm
Allele Name		targeted mutation 1.1, Jamey Marth
Allele Type		Targeted (knock-out)
Common Name(s)		ST3Gal-IV-; ST3Gal-IVdelta;
Mutation Made By		Jamey Marth,   Burnham Inst at Univ Calif Santa Barbara
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		St3gal4, ST3 beta-galactoside alpha-2,3-sialyltransferase 4
Chromosome		9
Gene Common Name(s)		CGS23; NANTA3; SAT3; SIAT4; SIAT4C; ST3Gal IV; ST3GalIV; STZ; Siat4c; sialyltransferase 4C (beta-galactoside alpha-2,3-sialytransferase);
Molecular Note		Exons 5 through 7 were initially flanked by an upstream floxed tk-neo cassette and a downstream single loxP site, then deleted via cre mediated recombination in ES cells. In addition to lacking sequence encoding the large sialyl motif necessary for nucleotide sugar binding and enzymatic activity, the allele passed into the germline also contained a frameshift mutation within exon 8. Transcript was undetected by Northern blot analysis of homozygous mutant mice. [MGI Ref ID J:80884]

Genotyping

Genotyping Information

Genotyping Protocols

St3gal4^tm1.1Jxm MCA, Melt Curve Analysis
St3gal4^tm1.1Jxm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ellies LG; Ditto D; Levy GG; Wahrenbrock M; Ginsburg D; Varki A; Le DT; Marth JD. 2002. Sialyltransferase ST3Gal-IV operates as a dominant modifier of hemostasis by concealing asialoglycoprotein receptor ligands. Proc Natl Acad Sci U S A 99(15):10042-7. [PubMed: 12097641]  [MGI Ref ID J:80884]

Additional References

St3gal4^tm1.1Jxm related

Ellies LG; Sperandio M; Underhill GH; Yousif J; Smith M; Priatel JJ; Kansas GS; Ley K; Marth JD. 2002. Sialyltransferase specificity in selectin ligand formation. Blood 100(10):3618-25. [PubMed: 12393657]  [MGI Ref ID J:80119]

Frommhold D; Ludwig A; Bixel MG; Zarbock A; Babushkina I; Weissinger M; Cauwenberghs S; Ellies LG; Marth JD; Beck-Sickinger AG; Sixt M; Lange-Sperandio B; Zernecke A; Brandt E; Weber C; Vestweber D; Ley K; Sperandio M. 2008. Sialyltransferase ST3Gal-IV controls CXCR2-mediated firm leukocyte arrest during inflammation. J Exp Med 205(6):1435-46. [PubMed: 18519646]  [MGI Ref ID J:137041]

Grewal PK; Uchiyama S; Ditto D; Varki N; Le DT; Nizet V; Marth JD. 2008. The Ashwell receptor mitigates the lethal coagulopathy of sepsis. Nat Med 14(6):648-55. [PubMed: 18488037]  [MGI Ref ID J:136946]

Nadeau JH. 2003. Modifier genes and protective alleles in humans and mice. Curr Opin Genet Dev 13(3):290-5. [PubMed: 12787792]  [MGI Ref ID J:88012]

Smith ML; Olson TS; Ley K. 2004. CXCR2- and E-selectin-induced neutrophil arrest during inflammation in vivo. J Exp Med 200(7):935-9. [PubMed: 15466624]  [MGI Ref ID J:93946]

Sperandio M; Frommhold D; Babushkina I; Ellies LG; Olson TS; Smith ML; Fritzsching B; Pauly E; Smith DF; Nobiling R; Linderkamp O; Marth JD; Ley K. 2006. Alpha2,3-sialyltransferase-IV is essential for L-selectin ligand function in inflammation. Eur J Immunol 36(12):3207-15. [PubMed: 17111351]  [MGI Ref ID J:117085]

Underhill GH; Zisoulis DG; Kolli KP; Ellies LG; Marth JD; Kansas GS. 2005. A crucial role for T-bet in selectin ligand expression in T helper 1 (Th1) cells. Blood 106(12):3867-73. [PubMed: 16099875]  [MGI Ref ID J:124068]

Wandall HH; Rumjantseva V; Sorensen AL; Patel-Hett S; Josefsson EC; Bennett EP; Italiano JE Jr; Clausen H; Hartwig JH; Hoffmeister KM. 2012. The origin and function of platelet glycosyltransferases. Blood 120(3):626-35. [PubMed: 22613794]  [MGI Ref ID J:189127]

Yang WH; Nussbaum C; Grewal PK; Marth JD; Sperandio M. 2012. Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands. Blood 120(5):1015-26. [PubMed: 22700726]  [MGI Ref ID J:189086]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygous crosses may be used.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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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.

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