Strain Name:

B6.129-Lcp2tm1Gak/J

Stock Number:

018860

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Availability:

Repository- Live

These Lcp2 knockout mice exhibit a complete loss of T cells and γδ-TCR+ lymphocytes, but maintain a normal number of B cells, macrophages, neutrophils, mast cells and NK cells. They may be useful for studies related to T cell development.

Description

Strain Information

Former Names B6;129-Lcp2tm1Gak/J    (Changed: 18-NOV-13 )
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 SystemWild-type x Heterozygote         (Female x Male)   28-JUL-13
Mating SystemHeterozygote x Wild-type         (Female x Male)   28-JUL-13
Specieslaboratory mouse
GenerationN?+pN1 (08-OCT-13)
Generation Definitions
 
Donating Investigator Gary Koretzky,   University of Pennsylvania

Description
SLP-76 is an immune cell adaptor expressed in T lymphocytes, macrophages, mast cells, platelets, neutrophils, and natural killer (NK) cells. It has been shown to play a role in lymphatic vascular development, T cell receptor (TCR) signaling, as well as signaling through receptors that use tyrosine base activation motifs in platelet, mast cells, neutrophils and NK cells. In these lymphocyte cytosolic protein 2 (Lcp2) knockout mice, a neomycin resistance cassette in reverse orientation disrupts the gene and abolishes Lcp2 expression. These mice have small lymph nodes and enlarged spleens when compared to controls. They exhibit a complete loss of T cells and γδ-TCR+ lymphocytes, but maintain a normal number of B cells, macrophages, neutrophils, mast cells and NK cells. Some homozygotes may be viable, but are born at a frequency lower than typical Mendelian ratios would predict. Substantial perinatal lethality is observed.

Development
A targeting vector was designed to replace 360 bp including exon 1 and the translational start site of the lymphocyte cytosolic protein 2 (Lcp2) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. 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 C57BL/6J blastocysts and the resulting chimeric males were bred to C57BL/6J females. The donating investigator reports that these mice were backcrossed for at least 10 generations to C57BL/6J mice (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Information

  Control
   Wild-type from the colony
   101043 B6129SF1/J
 
  Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Lcp2tm1Gak/Lcp2tm1Gak

        involves: 129S1/Sv * 129X1/SvJ
  • mortality/aging
  • partial perinatal lethality
    • there is a selective loss of homozygous progeny observed   (MGI Ref ID J:91369)
  • hematopoietic system phenotype
  • abnormal platelet activation
    • platelets fail to activate in response to plating on lymphatic microvascular endothelial cells (LEC) unlike wild-type cells   (MGI Ref ID J:162815)
    • platelets from neonates without vascular phenotypes exhibit low levels of convulxin-stimulated fibrinogen binding compared with similarly treated wild-type cells   (MGI Ref ID J:162815)
    • decreased platelet aggregation
      • platelets fail to form aggregates on microvascular endothelial cells (LEC) under flow unlike similarly treated wild-type cells   (MGI Ref ID J:162815)
  • homeostasis/metabolism phenotype
  • abnormal platelet activation
    • platelets fail to activate in response to plating on lymphatic microvascular endothelial cells (LEC) unlike wild-type cells   (MGI Ref ID J:162815)
    • platelets from neonates without vascular phenotypes exhibit low levels of convulxin-stimulated fibrinogen binding compared with similarly treated wild-type cells   (MGI Ref ID J:162815)
    • decreased platelet aggregation
      • platelets fail to form aggregates on microvascular endothelial cells (LEC) under flow unlike similarly treated wild-type cells   (MGI Ref ID J:162815)
View Research Applications

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

Developmental Biology Research
Embryonic Lethality (Homozygous)
      incomplete

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      T cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Lcp2tm1Gak
Allele Name targeted mutation 1, Gary A Koretzky
Allele Type Targeted (Null/Knockout)
Common Name(s) SLP-76-;
Mutation Made By Gary Koretzky,   University of Pennsylvania
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Lcp2, lymphocyte cytosolic protein 2
Chromosome 11
Gene Common Name(s) AI323664; BB161688; SLP-76; SLP76; expressed sequence AI323664; expressed sequence BB161688; t-wimp; twm;
Molecular Note Approximately 360 bp of the gene, including part of exon 1 and the translation initiation site, was replaced with a neo cassette via homologous recombination. RT-PCR analysis of homozygous mutant animals verified the absence of gene expression. Western blot and immunohistochemistry of spleen from homozygous mutant animals did not detect protein product. [MGI Ref ID J:76697]

Genotyping

Genotyping Information

Genotyping Protocols

Lcp2tm1Gak,

MELT



Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Clements JL; Yang B; Ross-Barta SE; Eliason SL; Hrstka RF; Williamson RA; Koretzky GA. 1998. Requirement for the leukocyte-specific adapter protein SLP-76 for normal T cell development. Science 281(5375):416-9. [PubMed: 9665885]  [MGI Ref ID J:76697]

Additional References

Lcp2tm1Gak related

Abtahian F; Bezman N; Clemens R; Sebzda E; Cheng L; Shattil SJ; Kahn ML; Koretzky GA. 2006. Evidence for the requirement of ITAM domains but not SLP-76/Gads interaction for integrin signaling in hematopoietic cells. Mol Cell Biol 26(18):6936-49. [PubMed: 16943434]  [MGI Ref ID J:112305]

Baker RG; Hsu CJ; Lee D; Jordan MS; Maltzman JS; Hammer DA; Baumgart T; Koretzky GA. 2009. The adapter protein SLP-76 mediates 'outside-in' integrin signaling and function in T cells. Mol Cell Biol 29(20):5578-89. [PubMed: 19667077]  [MGI Ref ID J:153901]

Bertozzi CC; Schmaier AA; Mericko P; Hess PR; Zou Z; Chen M; Chen CY; Xu B; Lu MM; Zhou D; Sebzda E; Santore MT; Merianos DJ; Stadtfeld M; Flake AW; Graf T; Skoda R; Maltzman JS; Koretzky GA; Kahn ML. 2010. Platelets regulate lymphatic vascular development through CLEC-2-SLP-76 signaling. Blood 116(4):661-70. [PubMed: 20363774]  [MGI Ref ID J:162815]

Bezman NA; Lian L; Abrams CS; Brass LF; Kahn ML; Jordan MS; Koretzky GA. 2008. Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo. J Exp Med 205(8):1775-88. [PubMed: 18663126]  [MGI Ref ID J:139532]

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]

Chen CY; Bertozzi C; Zou Z; Yuan L; Lee JS; Lu M; Stachelek SJ; Srinivasan S; Guo L; Vicente A; Mericko P; Levy RJ; Makinen T; Oliver G; Kahn ML. 2012. Blood flow reprograms lymphatic vessels to blood vessels. J Clin Invest 122(6):2006-17. [PubMed: 22622036]  [MGI Ref ID J:190484]

Chiang YJ; Jordan MS; Horai R; Schwartzberg PL; Koretzky GA; Hodes RJ. 2009. Cbl enforces an SLP76-dependent signaling pathway for T cell differentiation. J Biol Chem 284(7):4429-38. [PubMed: 19074136]  [MGI Ref ID J:147595]

Chiang YJ; Sommers CL; Jordan MS; Gu H; Samelson LE; Koretzky GA; Hodes RJ. 2004. Inactivation of c-Cbl Reverses Neonatal Lethality and T Cell Developmental Arrest of SLP-76-deficient Mice. J Exp Med 200(1):25-34. [PubMed: 15238603]  [MGI Ref ID J:91369]

Clements JL; Lee JR; Gross B; Yang B; Olson JD; Sandra A; Watson SP; Lentz SR; Koretzky GA. 1999. Fetal hemorrhage and platelet dysfunction in SLP-76-deficient mice. J Clin Invest 103(1):19-25. [PubMed: 9884330]  [MGI Ref ID J:51934]

Corbo-Rodgers E; Staub ES; Zou T; Smith A; Kambayashi T; Maltzman JS. 2012. Oral ivermectin as an unexpected initiator of CreT2-mediated deletion in T cells. Nat Immunol 13(3):197-8. [PubMed: 22344272]  [MGI Ref ID J:181643]

Judd BA; Myung PS; Leng L; Obergfell A; Pear WS; Shattil SJ; Koretzky GA. 2000. Hematopoietic reconstitution of SLP-76 corrects hemostasis and platelet signaling through alpha IIbbeta 3 and collagen receptors Proc Natl Acad Sci U S A 97(22):12056-61. [PubMed: 11050236]  [MGI Ref ID J:65381]

Judd BA; Myung PS; Obergfell A; Myers EE; Cheng AM; Watson SP; Pear WS; Allman D; Shattil SJ; Koretzky GA. 2002. Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. J Exp Med 195(6):705-17. [PubMed: 11901197]  [MGI Ref ID J:75708]

Kambayashi T; Okumura M; Baker RG; Hsu CJ; Baumgart T; Zhang W; Koretzky GA. 2010. Independent and cooperative roles of adaptor molecules in proximal signaling during FcepsilonRI-mediated mast cell activation. Mol Cell Biol 30(17):4188-96. [PubMed: 20606011]  [MGI Ref ID J:163285]

Lee D; Kim J; Baker RG; Koretzky GA; Hammer DA. 2012. SLP-76 is required for optimal CXCR4-stimulated T lymphocyte firm arrest to ICAM-1 under shear flow. Eur J Immunol 42(10):2736-43. [PubMed: 22806433]  [MGI Ref ID J:188001]

Leo L; Di Paola J; Judd BA; Koretzky GA; Lentz SR. 2002. Role of the adapter protein SLP-76 in GPVI-dependent platelet procoagulant responses to collagen. Blood 100(8):2839-44. [PubMed: 12351393]  [MGI Ref ID J:115518]

Liu X; Karnell JL; Yin B; Zhang R; Zhang J; Li P; Choi Y; Maltzman JS; Pear WS; Bassing CH; Turka LA. 2010. Distinct roles for PTEN in prevention of T cell lymphoma and autoimmunity in mice. J Clin Invest 120(7):2497-507. [PubMed: 20516645]  [MGI Ref ID J:163722]

Luckashenak NA; Ryszkiewicz RL; Ramsey KD; Clements JL. 2006. The Src homology 2 domain-containing leukocyte protein of 76-kDa adaptor links integrin ligation with p44/42 MAPK phosphorylation and podosome distribution in murine dendritic cells. J Immunol 177(8):5177-85. [PubMed: 17015703]  [MGI Ref ID J:139449]

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]

Michie AM; Chan AC; Ciofani M; Carleton M; Lefebvre JM; He Y; Allman DM; Wiest DL; Zuniga-Pflucker JC; Izon DJ. 2007. Constitutive Notch signalling promotes CD4 CD8 thymocyte differentiation in the absence of the pre-TCR complex, by mimicking pre-TCR signals. Int Immunol 19(12):1421-30. [PubMed: 17981791]  [MGI Ref ID J:127831]

Nichols KE; Haines K; Myung PS; Newbrough S; Myers E; Jumaa H; Shedlock DJ; Shen H; Koretzky GA. 2004. Macrophage activation and Fcgamma receptor-mediated signaling do not require expression of the SLP-76 and SLP-65 adaptors. J Leukoc Biol 75(3):541-52. [PubMed: 14694181]  [MGI Ref ID J:88628]

Pedraza-Alva G; Koulnis M; Charland C; Thornton T; Clements JL; Schlissel MS; Rincon M. 2006. Activation of p38 MAP kinase by DNA double-strand breaks in V(D)J recombination induces a G2/M cell cycle checkpoint. EMBO J 25(4):763-73. [PubMed: 16456545]  [MGI Ref ID J:105987]

Peterson EJ; Clements JL; Ballas ZK; Koretzky GA. 1999. NK cytokine secretion and cytotoxicity occur independently of the SLP-76 adaptor protein. Eur J Immunol 29(7):2223-32. [PubMed: 10427985]  [MGI Ref ID J:56584]

Ramsey K; Luckashenak N; Koretzky GA; Clements JL. 2008. Impaired thymic selection in mice expressing altered levels of the SLP-76 adaptor protein. J Leukoc Biol 83(2):419-29. [PubMed: 17965338]  [MGI Ref ID J:131225]

Reeve JL; Zou W; Liu Y; Maltzman JS; Ross FP; Teitelbaum SL. 2009. SLP-76 couples Syk to the osteoclast cytoskeleton. J Immunol 183(3):1804-12. [PubMed: 19592646]  [MGI Ref ID J:151601]

Sarratt KL; Chen H; Zutter MM; Santoro SA; Hammer DA; Kahn ML. 2005. GPVI and alpha2beta1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood 106(4):1268-77. [PubMed: 15886326]  [MGI Ref ID J:117300]

Sebzda E; Hibbard C; Sweeney S; Abtahian F; Bezman N; Clemens G; Maltzman JS; Cheng L; Liu F; Turner M; Tybulewicz V; Koretzky GA; Kahn ML. 2006. Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev Cell 11(3):349-61. [PubMed: 16950126]  [MGI Ref ID J:112805]

Wiehagen KR; Corbo E; Schmidt M; Shin H; Wherry EJ; Maltzman JS. 2010. Loss of tonic T-cell receptor signals alters the generation but not the persistence of CD8+ memory T cells. Blood 116(25):5560-70. [PubMed: 20884806]  [MGI Ref ID J:167386]

Wu GF; Corbo E; Schmidt M; Smith-Garvin JE; Riese MJ; Jordan MS; Laufer TM; Brown EJ; Maltzman JS. 2011. Conditional deletion of SLP-76 in mature T cells abrogates peripheral immune responses. Eur J Immunol 41(7):2064-73. [PubMed: 21469089]  [MGI Ref ID J:177316]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, heterozygous mice may be bred together. The donating investigator reports that homozygotes are viable but born at a frequency lower than Mendelian, with substantial perinatal lethality.
Mating SystemWild-type x Heterozygote         (Female x Male)   28-JUL-13
Heterozygote x Wild-type         (Female x Male)   28-JUL-13
Diet Information LabDiet® 5K20

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHeterozygous for Lcp2tm1Gak  
Price per Pair (US dollars $)Pair Genotype
$271.90Heterozygous for Lcp2tm1Gak x Wild-type for Lcp2tm1Gak  
$271.90Wild-type for Lcp2tm1Gak x Heterozygous for Lcp2tm1Gak  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHeterozygous for Lcp2tm1Gak  
Price per Pair (US dollars $)Pair Genotype
$353.50Heterozygous for Lcp2tm1Gak x Wild-type for Lcp2tm1Gak  
$353.50Wild-type for Lcp2tm1Gak x Heterozygous for Lcp2tm1Gak  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
   101043 B6129SF1/J
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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