Strain Name:

B6.129-Fybtm1Gak/J

Stock Number:

018862

Availability:

Awaiting Transfer from the Donor

Use Restrictions Apply, see Terms of Use
Register Interest
These Fyb knockout mice display defective T cell receptor-mediated adhesion and aggregation. They may have applications in studies related to leukocyte recruitment.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Gary Koretzky,   University of Pennsylvania

Description
A neo cassette replaces exon 1 of the FYN binding protein (Fyb) gene, abolishing gene expression. FYB, also known as ADAP (adhesion and degranulation promoting adaptor protein), is expressed in various hematopoietic cell types and is required for slow leukocyte rolling and leukocyte recruitment to areas of inflammation. The number of T cells in these mice is decreased and they display defective T cell receptor (TCR)-mediated adhesion and aggregation. These mice also have decreased numbers of platelets and leukocytes. Homozygotes are viable and fertile.

Development
A targeting vector was designed to replace exon 1 of the FYN binding protein (Fyb) gene with a neomycin resistance (neo) cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6 females. These mice were backcrossed 10 generations to C57BL/6 mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Information

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

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Fybtm1Gak/Fybtm1Gak

        B6.129-Fybtm1Gak
  • immune system phenotype
  • *normal* immune system phenotype
    • despite the expression of Fyb in NK cells, NK cell numbers and and functions are unaffected in homozygotes   (MGI Ref ID J:112087)

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

Fybtm1Gak/Fybtm1Gak

        involves: 129S1/Sv * 129X1/SvJ
  • immune system phenotype
  • abnormal T cell physiology
    • in response to stimulation, T cells exhibit decreased aggregation compared to wild-type cells   (MGI Ref ID J:126545)
    • adhesion of stimulated T cells to ICAM1 is reduced compared to that of wild-type cells   (MGI Ref ID J:126545)
    • however, normal ICAM binding can be restored with high levels of stimulation of anti-CD3 antibodies   (MGI Ref ID J:126545)
    • decreased T cell proliferation
      • in response to anti-CD3epsilon   (MGI Ref ID J:111368)
      • proliferation of stimulated T cells is reduced compared to in wild-type mice   (MGI Ref ID J:126545)
      • however, normal proliferation can be restored with high levels of stimulation of anti-CD3 antibodies   (MGI Ref ID J:126545)
  • abnormal leukocyte adhesion
    • unlike in wild-type mice, there is no increase in adhesion following TCR stimulation   (MGI Ref ID J:111368)
    • however, treatement with phorbol 12-myristate 13-acetate (PMA) or Mn2+ does increase adhesion as it does in wild-type   (MGI Ref ID J:111368)
  • decreased interleukin-2 secretion   (MGI Ref ID J:126545)
    • reduction in the production of IL-2 following anti-CD3epsilon stimulation   (MGI Ref ID J:111368)
  • decreased thymocyte number
    • 188+/-66x106 compared to 254+/-88x106 in wild-type mice   (MGI Ref ID J:111368)
  • hematopoietic system phenotype
  • abnormal T cell physiology
    • in response to stimulation, T cells exhibit decreased aggregation compared to wild-type cells   (MGI Ref ID J:126545)
    • adhesion of stimulated T cells to ICAM1 is reduced compared to that of wild-type cells   (MGI Ref ID J:126545)
    • however, normal ICAM binding can be restored with high levels of stimulation of anti-CD3 antibodies   (MGI Ref ID J:126545)
    • decreased T cell proliferation
      • in response to anti-CD3epsilon   (MGI Ref ID J:111368)
      • proliferation of stimulated T cells is reduced compared to in wild-type mice   (MGI Ref ID J:126545)
      • however, normal proliferation can be restored with high levels of stimulation of anti-CD3 antibodies   (MGI Ref ID J:126545)
  • abnormal leukocyte adhesion
    • unlike in wild-type mice, there is no increase in adhesion following TCR stimulation   (MGI Ref ID J:111368)
    • however, treatement with phorbol 12-myristate 13-acetate (PMA) or Mn2+ does increase adhesion as it does in wild-type   (MGI Ref ID J:111368)
  • decreased platelet cell number
    • 410+/-74x103 compared to 721+/-275x103 in wild-type mice   (MGI Ref ID J:111368)
  • decreased thymocyte number
    • 188+/-66x106 compared to 254+/-88x106 in wild-type mice   (MGI Ref ID J:111368)
  • cellular phenotype
  • abnormal leukocyte adhesion
    • unlike in wild-type mice, there is no increase in adhesion following TCR stimulation   (MGI Ref ID J:111368)
    • however, treatement with phorbol 12-myristate 13-acetate (PMA) or Mn2+ does increase adhesion as it does in wild-type   (MGI Ref ID J:111368)
View Research Applications

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

Cardiovascular Research
Vascular Defects
      defective leukocyte function

Cell Biology Research
Defects in Cell Adhesion Molecules

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Fybtm1Gak
Allele Name targeted mutation 1, Gary A Koretzky
Allele Type Targeted (knock-out)
Common Name(s) ADAP-; Fyb-;
Mutation Made By Gary Koretzky,   University of Pennsylvania
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Fyb, FYN binding protein
Chromosome 15
Gene Common Name(s) ADAP; B630013F22Rik; FYB-120/130; PRO0823; RGD1563421; RIKEN cDNA B630013F22 gene; SLAP-130;
Molecular Note Exon 1 was replaced with a neomycin resistance cassette. [MGI Ref ID J:111368]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Peterson EJ; Woods ML; Dmowski SA; Derimanov G; Jordan MS; Wu JN; Myung PS; Liu QH; Pribila JT; Freedman BD; Shimizu Y; Koretzky GA. 2001. Coupling of the TCR to integrin activation by Slap-130/Fyb. Science 293(5538):2263-5. [PubMed: 11567141]  [MGI Ref ID J:111368]

Additional References

Fybtm1Gak related

Block H; Herter JM; Rossaint J; Stadtmann A; Kliche S; Lowell CA; Zarbock A. 2012. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury. J Exp Med 209(2):407-21. [PubMed: 22291096]  [MGI Ref ID J:181695]

Burbach BJ; Srivastava R; Medeiros RB; O'Gorman WE; Peterson EJ; Shimizu Y. 2008. Distinct regulation of integrin-dependent T cell conjugate formation and NF-kappa B activation by the adapter protein ADAP. J Immunol 181(7):4840-51. [PubMed: 18802088]  [MGI Ref ID J:142742]

Burns JC; Corbo E; Degen J; Gohil M; Anterasian C; Schraven B; Koretzky GA; Kliche S; Jordan MS. 2011. The SLP-76 Src homology 2 domain is required for T cell development and activation. J Immunol 187(9):4459-66. [PubMed: 21949020]  [MGI Ref ID J:179442]

Dluzniewska J; Zou L; Harmon IR; Ellingson MT; Peterson EJ. 2007. Immature hematopoietic cells display selective requirements for adhesion- and degranulation-promoting adaptor protein in development and homeostatsis. Eur J Immunol 37(11):3208-19. [PubMed: 17948263]  [MGI Ref ID J:126331]

Engelmann S; Togni M; Thielitz A; Reichardt P; Kliche S; Reinhold D; Schraven B; Reinhold A. 2013. T cell-independent modulation of experimental autoimmune encephalomyelitis in ADAP-deficient mice. J Immunol 191(10):4950-9. [PubMed: 24101551]  [MGI Ref ID J:206334]

Fostel LV; Dluzniewska J; Shimizu Y; Burbach BJ; Peterson EJ. 2006. ADAP is dispensable for NK cell development and function. Int Immunol 18(8):1305-14. [PubMed: 16775024]  [MGI Ref ID J:112087]

Kasirer-Friede A; Moran B; Nagrampa-Orje J; Swanson K; Ruggeri ZM; Schraven B; Neel BG; Koretzky G; Shattil SJ. 2007. ADAP is required for normal alphaIIbbeta3 activation by VWF/GP Ib-IX-V and other agonists. Blood 109(3):1018-25. [PubMed: 17003372]  [MGI Ref ID J:144396]

Kasirer-Friede A; Ruggeri ZM; Shattil SJ. 2010. Role for ADAP in shear flow-induced platelet mechanotransduction. Blood 115(11):2274-82. [PubMed: 19996090]  [MGI Ref ID J:158859]

Kliche S; Worbs T; Wang X; Degen J; Patzak I; Meineke B; Togni M; Moser M; Reinhold A; Kiefer F; Freund C; Forster R; Schraven B. 2012. CCR7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP/SKAP55 modules. Blood 119(3):777-85. [PubMed: 22117043]  [MGI Ref ID J:181785]

May RM; Okumura M; Hsu CJ; Bassiri H; Yang E; Rak G; Mace EM; Philip NH; Zhang W; Baumgart T; Orange JS; Nichols KE; Kambayashi T. 2013. Murine natural killer immunoreceptors use distinct proximal signaling complexes to direct cell function. Blood 121(16):3135-46. [PubMed: 23407547]  [MGI Ref ID J:196459]

Mitchell JS; Burbach BJ; Srivastava R; Fife BT; Shimizu Y. 2013. Multistage T cell-dendritic cell interactions control optimal CD4 T cell activation through the ADAP-SKAP55-signaling module. J Immunol 191(5):2372-83. [PubMed: 23918975]  [MGI Ref ID J:205802]

Mueller KL; Thomas MS; Burbach BJ; Peterson EJ; Shimizu Y. 2007. Adhesion and degranulation-promoting adapter protein (ADAP) positively regulates T cell sensitivity to antigen and T cell survival. J Immunol 179(6):3559-69. [PubMed: 17785790]  [MGI Ref ID J:142998]

Srivastava R; Burbach BJ; Mitchell JS; Pagan AJ; Shimizu Y. 2012. ADAP regulates cell cycle progression of T cells via control of cyclin E and Cdk2 expression through two distinct CARMA1-dependent signaling pathways. Mol Cell Biol 32(10):1908-17. [PubMed: 22411628]  [MGI Ref ID J:185746]

Srivastava R; Burbach BJ; Shimizu Y. 2010. NF-kappaB activation in T cells requires discrete control of IkappaB kinase alpha/beta (IKKalpha/beta) phosphorylation and IKKgamma ubiquitination by the ADAP adapter protein. J Biol Chem 285(15):11100-5. [PubMed: 20164171]  [MGI Ref ID J:161173]

Suzuki J; Yamasaki S; Wu J; Koretzky GA; Saito T. 2007. The actin cloud induced by LFA-1-mediated outside-in signals lowers the threshold for T-cell activation. Blood 109(1):168-75. [PubMed: 16973965]  [MGI Ref ID J:142177]

Wang H; Liu H; Lu Y; Lovatt M; Wei B; Rudd CE. 2007. Functional defects of SKAP-55-deficient T cells identify a regulatory role for the adaptor in LFA-1 adhesion. Mol Cell Biol 27(19):6863-75. [PubMed: 17646386]  [MGI Ref ID J:126545]

Wu JN; Gheith S; Bezman NA; Liu QH; Fostel LV; Swanson AM; Freedman BD; Koretzky GA; Peterson EJ. 2006. Adhesion- and degranulation-promoting adapter protein is required for efficient thymocyte development and selection. J Immunol 176(11):6681-9. [PubMed: 16709827]  [MGI Ref ID J:131800]

Zou L; Mendez F; Martin-Orozco N; Peterson EJ. 2008. Defective positive selection results in T cell lymphopenia and increased autoimmune diabetes in ADAP-deficient BDC2.5-C57BL/6 mice. Eur J Immunol 38(4):986-94. [PubMed: 18383041]  [MGI Ref ID J:133782]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently Awaiting Transfer from the Donor.

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Control Information

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

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