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)   31-OCT-06 Species laboratory mouse Generation [N9+?F1pN1]+F15 (16-SEP-12) Generation Definitions   Donating Investigator Andrew D Luster,   Massachusetts General Hospital-East

Description
Homozygous mice are viable, fertile, and have no overt morphological or developmental abnormalities. No endogenous gene expression is observed in bone marrow-derived macrophages before or after IFN-gamma stimulation. Homozygous mice have defective T cell responses, including impaired proliferation and IFN-gamma secretion following antigenic challenge (129Sv background). In experimental models of T helper-1 (Th1)-mediated immune responses, homozygous-deletion leads to diminished immune function; contact hypersensitivity is reduced (129Sv background) and diminished threshold for disease expression in experimental autoimmune encephalomyelitis (EAE, human model of multiple sclerosis) (C57BL/6 background). After injection with a neurotropic coronavirus MHV, null mice (on a B6;129Sv background) exhibit impaired viral clearance, decreased CD4⁺/CD8⁺ infiltration into the brain, and are protected from viral-induced demyelination. Similarly, homozygous mice (on a C57BL/6 background) infected with West Nile Virus have increased viral load in brain, altered CD8⁺ effector T cell recruitment to neurons and increased mortality. These mutant mice may be useful in studies of Th1-type inflammatory disease, chemokine biology, and T cell priming, proliferation, and trafficking.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for this strain. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing a mouse phosphoglycerate kinase promoter driven neomycin resistance gene was used to replace exons 1-3 of the endogenous gene. The construct was electroporated into the 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric mice were bred to C57BL/6 to generate mice heterozygous for the mutant allele. Mutant mice were mated to C57BL/6 mice for 9 generations and then made homozygous before arriving at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Cxcl10^tm1Adl allele

006134

C.129S4(B6)-Cxcl10tm1Adl/J

View Strains carrying   Cxcl10^tm1Adl     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Cxcl10^tm1Adl/Cxcl10^tm1Adl

        B6.129S4-Cxcl10^tm1Adl

• immune system phenotype
• CNS inflammation
  • experimental autoimmune encephalomyelitis involves meningeal and brain parenchyma after 15 days   (MGI Ref ID J:87076)
  • monocytes lymphocytes and some granulocytes are involved   (MGI Ref ID J:87076)
  • increased levels of IFN-gamma, Il-2 and TGF-Beta1 in lymph nodes   (MGI Ref ID J:87076)
• abnormal cytokine secretion
  • only CCL2 levels are elevated in corneas relative to wild-type or Cxcl9-null mice after HSV-1 infection   (MGI Ref ID J:120743)
• increased susceptibility to experimental autoimmune encephalomyelitis
  • higher incidence and greater severity of experimental autoimmune encephalomyelitis   (MGI Ref ID J:87076)
• increased susceptibility to viral infection
  • 7 days after infection (day 7 pi) with herpes simplex virus type I (HSV-1), homozygotes have significantly higher HSV-1 titers in the cornea compared to Cxcl9-null or wild-type mice   (MGI Ref ID J:120743)
  • virus shedding in the tear film is elevated at day 7 pi but not at early points relative to Cxcl9 homozygotes or wild-type controls   (MGI Ref ID J:120743)
  • mice usually succumb to infection between days 7 and 9 pi   (MGI Ref ID J:120743)
• nervous system phenotype
• CNS inflammation
  • experimental autoimmune encephalomyelitis involves meningeal and brain parenchyma after 15 days   (MGI Ref ID J:87076)
  • monocytes lymphocytes and some granulocytes are involved   (MGI Ref ID J:87076)
  • increased levels of IFN-gamma, Il-2 and TGF-Beta1 in lymph nodes   (MGI Ref ID J:87076)

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

Cxcl10^tm1Adl/Cxcl10^tm1Adl

        involves: 129S4/SvJae * 129X1/SvJ

• immune system phenotype
• decreased IgG2a level
  • reduced levels of antigen specific IgG2a in serum when immunized with OVA   (MGI Ref ID J:75584)
• decreased interferon-gamma secretion
  • secretion of IFN-gamma reduced 60%   (MGI Ref ID J:75584)
• decreased splenocyte proliferation
  • splenocytes display significantly reduced proliferative responses in mixed lymphocyte reactions using MHC antigens but not when using conA   (MGI Ref ID J:75584)
  • proliferative responses after sensitization to specific antigens is also reduced   (MGI Ref ID J:75584)
• decreased susceptibility to type IV hypersensitivity reaction
  • reduced contact hypersensitivity   (MGI Ref ID J:75584)
• hematopoietic system phenotype
• decreased splenocyte proliferation
  • splenocytes display significantly reduced proliferative responses in mixed lymphocyte reactions using MHC antigens but not when using conA   (MGI Ref ID J:75584)
  • proliferative responses after sensitization to specific antigens is also reduced   (MGI Ref ID J:75584)
• cellular phenotype
• decreased splenocyte proliferation
  • splenocytes display significantly reduced proliferative responses in mixed lymphocyte reactions using MHC antigens but not when using conA   (MGI Ref ID J:75584)
  • proliferative responses after sensitization to specific antigens is also reduced   (MGI Ref ID J:75584)

Cxcl10^tm1Adl/Cxcl10^tm1Adl

        involves: 129S4/SvJae * C57BL/6

• immune system phenotype
• abnormal T cell physiology
  • decreased CNS levels of both CD4+ and CD8+ T cells after mouse hepatitis virus infection   (MGI Ref ID J:75584)
• abnormal interferon level
  • decreased IFN-gamma in response to mouse hepatitis virus   (MGI Ref ID J:75584)
• decreased CD8-positive T cell number
  • 25% decrease in the spleen after mouse hepatitis virus infection   (MGI Ref ID J:75584)
• increased susceptibility to viral infection
  • greater sensitivity to mouse hepatitis virus   (MGI Ref ID J:75584)
  • titers similar to controls after 7 days but significantly higher than controls 12 days after infection   (MGI Ref ID J:75584)
• nervous system phenotype
• demyelination
  • level of demyelination reduced 12 days after infection with mouse hepatitis virus   (MGI Ref ID J:75584)
• hematopoietic system phenotype
• decreased CD8-positive T cell number
  • 25% decrease in the spleen after mouse hepatitis virus infection   (MGI Ref ID J:75584)
• homeostasis/metabolism phenotype
• abnormal interferon level
  • decreased IFN-gamma in response to mouse hepatitis virus   (MGI Ref ID J:75584)

View Research Applications

Research Applications

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

Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction
Transcriptional Regulation

Immunology, Inflammation and Autoimmunity Research
Autoimmunity
      experimental allergic encephalomyelitis (EAE)
CD Antigens, Antigen Receptors, and Histocompatibility Markers
      genes regulating susceptibility to infectious disease and endotoxin
Growth Factors/Receptors/Cytokines
Immunodeficiency
      T cell deficiency
      specific T cell deficiency
Immunodeficiency Associated with Other Defects

Research Tools
Cell Biology Research
Immunology and Inflammation Research
      T cell deficiency
      genes regulating susceptibility to infectious disease and endotoxin
      specific T cell deficiency

Virology Research
B and T Cell Deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Cxcl10tm1Adl
Allele Name		targeted mutation 1, Andrew D Luster
Allele Type		Targeted (knock-out)
Common Name(s)		IP-10-;
Mutation Made By		Andrew Luster,   Massachusetts General Hospital-East
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Cxcl10, chemokine (C-X-C motif) ligand 10
Chromosome		5
Gene Common Name(s)		C7; CRG-2; IFI10; INP10; IP-10; IP10; Ifi10; SCYB10; Scyb10; gIP-10; interferon activated gene 10; mob-1; small inducible cytokine B subfamily (Cys-X-Cys), member 10;
Molecular Note		Exons 1-3, which encompass most of the coding region of the gene, were replaced with a PGK-neo cassette via homologous recombination. Northern and Western blot analyses of bone marrow macrophages confirmed the absence of gene expression in homozygous mutant animals. [MGI Ref ID J:75584]

Genotyping

Genotyping Information

Genotyping Protocols

Cxcl10^tm1Adl MCA SEP, Melt Curve Analysis
Cxcl10^tm1Adl, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Dufour JH; Dziejman M; Liu MT; Leung JH; Lane TE; Luster AD. 2002. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168(7):3195-204. [PubMed: 11907072]  [MGI Ref ID J:75584]

Additional References

Cxcl10^tm1Adl related

Auerbach MB; Shimoda N; Amano H; Rosenblum JM; Kish DD; Farber JM; Fairchild RL. 2009. Monokine induced by interferon-gamma (MIG/CXCL9) is derived from both donor and recipient sources during rejection of class II major histocompatibility complex disparate skin allografts. Am J Pathol 174(6):2172-81. [PubMed: 19389928]  [MGI Ref ID J:148781]

Bujak M; Dobaczewski M; Gonzalez-Quesada C; Xia Y; Leucker T; Zymek P; Veeranna V; Tager AM; Luster AD; Frangogiannis NG. 2009. Induction of the CXC chemokine interferon-gamma-inducible protein 10 regulates the reparative response following myocardial infarction. Circ Res 105(10):973-83. [PubMed: 19797174]  [MGI Ref ID J:169950]

Campanella GS; Tager AM; El Khoury JK; Thomas SY; Abrazinski TA; Manice LA; Colvin RA; Luster AD. 2008. Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the development of murine cerebral malaria. Proc Natl Acad Sci U S A 105(12):4814-9. [PubMed: 18347328]  [MGI Ref ID J:133359]

Christensen JE; Simonsen S; Fenger C; Sorensen MR; Moos T; Christensen JP; Finsen B; Thomsen AR. 2009. Fulminant lymphocytic choriomeningitis virus-induced inflammation of the CNS involves a cytokine-chemokine-cytokine-chemokine cascade. J Immunol 182(2):1079-87. [PubMed: 19124751]  [MGI Ref ID J:143550]

Christensen JE; de Lemos C; Moos T; Christensen JP; Thomsen AR. 2006. CXCL10 is the key ligand for CXCR3 on CD8+ effector T cells involved in immune surveillance of the lymphocytic choriomeningitis virus-infected central nervous system. J Immunol 176(7):4235-43. [PubMed: 16547260]  [MGI Ref ID J:129874]

Fujita M; Zhu X; Ueda R; Sasaki K; Kohanbash G; Kastenhuber ER; McDonald HA; Gibson GA; Watkins SC; Muthuswamy R; Kalinski P; Okada H. 2009. Effective immunotherapy against murine gliomas using type 1 polarizing dendritic cells--significant roles of CXCL10. Cancer Res 69(4):1587-95. [PubMed: 19190335]  [MGI Ref ID J:146507]

Groom JR; Richmond J; Murooka TT; Sorensen EW; Sung JH; Bankert K; von Andrian UH; Moon JJ; Mempel TR; Luster AD. 2012. CXCR3 Chemokine Receptor-Ligand Interactions in the Lymph Node Optimize CD4(+) T Helper 1 Cell Differentiation. Immunity 37(6):1091-103. [PubMed: 23123063]  [MGI Ref ID J:191089]

Hamrah P; Yamagami S; Liu Y; Zhang Q; Vora SS; Lu B; Gerard CJ; Dana MR. 2007. Deletion of the chemokine receptor CCR1 prolongs corneal allograft survival. Invest Ophthalmol Vis Sci 48(3):1228-36. [PubMed: 17325167]  [MGI Ref ID J:123260]

Heller EA; Liu E; Tager AM; Yuan Q; Lin AY; Ahluwalia N; Jones K; Koehn SL; Lok VM; Aikawa E; Moore KJ; Luster AD; Gerszten RE. 2006. Chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T cells. Circulation 113(19):2301-12. [PubMed: 16682613]  [MGI Ref ID J:122449]

Hsieh MF; Lai SL; Chen JP; Sung JM; Lin YL; Wu-Hsieh BA; Gerard C; Luster A; Liao F. 2006. Both CXCR3 and CXCL10/IFN-inducible protein 10 are required for resistance to primary infection by dengue virus. J Immunol 177(3):1855-63. [PubMed: 16849497]  [MGI Ref ID J:137997]

Ip PP; Liao F. 2010. Resistance to dengue virus infection in mice is potentiated by CXCL10 and is independent of CXCL10-mediated leukocyte recruitment. J Immunol 184(10):5705-14. [PubMed: 20400703]  [MGI Ref ID J:160993]

Israelsson C; Bengtsson H; Lobell A; Nilsson LN; Kylberg A; Isaksson M; Wootz H; Lannfelt L; Kullander K; Hillered L; Ebendal T. 2010. Appearance of Cxcl10-expressing cell clusters is common for traumatic brain injury and neurodegenerative disorders. Eur J Neurosci 31(5):852-63. [PubMed: 20374285]  [MGI Ref ID J:159617]

Kastenmuller W; Brandes M; Wang Z; Herz J; Egen JG; Germain RN. 2013. Peripheral Prepositioning and Local CXCL9 Chemokine-Mediated Guidance Orchestrate Rapid Memory CD8(+) T Cell Responses in the Lymph Node. Immunity 38(3):502-13. [PubMed: 23352234]  [MGI Ref ID J:194479]

King VL; Lin AY; Kristo F; Anderson TJ; Ahluwalia N; Hardy GJ; Owens AP 3rd; Howatt DA; Shen D; Tager AM; Luster AD; Daugherty A; Gerszten RE. 2009. Interferon-gamma and the interferon-inducible chemokine CXCL10 protect against aneurysm formation and rupture. Circulation 119(3):426-35. [PubMed: 19139386]  [MGI Ref ID J:166204]

Klein RS; Izikson L; Means T; Gibson HD; Lin E; Sobel RA; Weiner HL; Luster AD. 2004. IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis. J Immunol 172(1):550-9. [PubMed: 14688366]  [MGI Ref ID J:87076]

Klein RS; Lin E; Zhang B; Luster AD; Tollett J; Samuel MA; Engle M; Diamond MS. 2005. Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis. J Virol 79(17):11457-66. [PubMed: 16103196]  [MGI Ref ID J:101771]

Lee JH; Kim HN; Kim KO; Jin WJ; Lee S; Kim HH; Ha H; Lee ZH. 2012. CXCL10 promotes osteolytic bone metastasis by enhancing cancer outgrowth and osteoclastogenesis. Cancer Res 72(13):3175-86. [PubMed: 22562465]  [MGI Ref ID J:189315]

Liu M; Amodu AS; Pitts S; Patrickson J; Hibbert JM; Battle M; Ofori-Acquah SF; Stiles JK. 2012. Heme mediated STAT3 activation in severe malaria. PLoS One 7(3):e34280. [PubMed: 22479586]  [MGI Ref ID J:187123]

Medoff BD; Sauty A; Tager AM; Maclean JA; Smith RN; Mathew A; Dufour JH; Luster AD. 2002. IFN-gamma-inducible protein 10 (CXCL10) contributes to airway hyperreactivity and airway inflammation in a mouse model of asthma. J Immunol 168(10):5278-86. [PubMed: 11994485]  [MGI Ref ID J:125569]

Medoff BD; Wain JC; Seung E; Jackobek R; Means TK; Ginns LC; Farber JM; Luster AD. 2006. CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. J Immunol 176(11):7087-95. [PubMed: 16709871]  [MGI Ref ID J:131767]

Peng W; Liu C; Xu C; Lou Y; Chen J; Yang Y; Yagita H; Overwijk WW; Lizee G; Radvanyi L; Hwu P. 2012. PD-1 blockade enhances T-cell migration to tumors by elevating IFN-gamma inducible chemokines. Cancer Res 72(20):5209-18. [PubMed: 22915761]  [MGI Ref ID J:191805]

Pociask DA; Chen K; Mi Choi S; Oury TD; Steele C; Kolls JK. 2011. gammadelta T Cells Attenuate Bleomycin-Induced Fibrosis through the Production of CXCL10. Am J Pathol 178(3):1167-76. [PubMed: 21356368]  [MGI Ref ID J:169690]

Rosenblum JM; Shimoda N; Schenk AD; Zhang H; Kish DD; Keslar K; Farber JM; Fairchild RL. 2010. CXC chemokine ligand (CXCL) 9 and CXCL10 are antagonistic costimulation molecules during the priming of alloreactive T cell effectors. J Immunol 184(7):3450-60. [PubMed: 20194716]  [MGI Ref ID J:160084]

Stiles LN; Hardison JL; Schaumburg CS; Whitman LM; Lane TE. 2006. T cell antiviral effector function is not dependent on CXCL10 following murine coronavirus infection. J Immunol 177(12):8372-80. [PubMed: 17142734]  [MGI Ref ID J:140673]

Tager AM; Kradin RL; LaCamera P; Bercury SD; Campanella GS; Leary CP; Polosukhin V; Zhao LH; Sakamoto H; Blackwell TS; Luster AD. 2004. Inhibition of pulmonary fibrosis by the chemokine IP-10/CXCL10. Am J Respir Cell Mol Biol 31(4):395-404. [PubMed: 15205180]  [MGI Ref ID J:133071]

Thapa M; Carr DJ. 2008. Herpes simplex virus type 2-induced mortality following genital infection is blocked by anti-tumor necrosis factor alpha antibody in CXCL10-deficient mice. J Virol 82(20):10295-301. [PubMed: 18684827]  [MGI Ref ID J:140202]

Thapa M; Welner RS; Pelayo R; Carr DJ. 2008. CXCL9 and CXCL10 expression are critical for control of genital herpes simplex virus type 2 infection through mobilization of HSV-specific CTL and NK cells to the nervous system. J Immunol 180(2):1098-106. [PubMed: 18178850]  [MGI Ref ID J:130943]

Wuest T; Farber J; Luster A; Carr DJ. 2006. CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection. Cell Immunol 243(2):83-9. [PubMed: 17296171]  [MGI Ref ID J:120743]

Wuest TR; Carr DJ. 2008. Dysregulation of CXCR3 signaling due to CXCL10 deficiency impairs the antiviral response to herpes simplex virus 1 infection. J Immunol 181(11):7985-93. [PubMed: 19017990]  [MGI Ref ID J:142374]

Zhang B; Chan YK; Lu B; Diamond MS; Klein RS. 2008. CXCR3 mediates region-specific antiviral T cell trafficking within the central nervous system during West Nile virus encephalitis. J Immunol 180(4):2641-9. [PubMed: 18250476]  [MGI Ref ID J:131972]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)   31-OCT-06
Diet Information	LabDiet® 5K52/5K67

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.

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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.

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.

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Terms of Use

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General Terms and Conditions

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phone:	207-288-6470
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