Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Andrew 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 allele s 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. Chimeric mice were bred to C57BL/6 generate a mutant colony. Mutant mice were then mated to BALB/c for 9 generations and then made homozygous before arriving at The Jackson Laboratory.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls

Related Strains

Strains carrying   Cxcl10^tm1Adl allele

006087

B6.129S4-Cxcl10tm1Adl/J

View Strains carrying   Cxcl10^tm1Adl     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Cxcl10^tm1Adl/Cxcl10^tm1Adl

        involves: 129S4/SvJae * C57BL/6

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

Cxcl10^tm1Adl/Cxcl10^tm1Adl

        B6.129S4-Cxcl10^tm1Adl

• immune system phenotype
• CNS inflammation (MGI Ref ID J:87076)
  • experimental autoimmune encephalomyelitis involves meningeal and brain parenchyma after 15 days
  • monocytes lymphocytes and some granulocytes are involved
  • increased levels of IFN-gamma, Il-2 and TGF-Beta1 in lymph nodes
• abnormal cytokine secretion (MGI Ref ID J:120743)
  • only CCL2 levels are elevated in corneas relative to wild-type or Cxcl9-null mice after HSV-1 infection
• increased susceptibility to experimental autoimmune encephalomyelitis (MGI Ref ID J:87076)
  • higher incidence and greater severity of experimental autoimmune encephalomyelitis
• increased susceptibility to viral infection (MGI Ref ID J:120743)
  • 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
  • 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
  • mice usually succumb to infection between days 7 and 9 pi
• nervous system phenotype
• CNS inflammation (MGI Ref ID J:87076)
  • experimental autoimmune encephalomyelitis involves meningeal and brain parenchyma after 15 days
  • monocytes lymphocytes and some granulocytes are involved
  • increased levels of IFN-gamma, Il-2 and TGF-Beta1 in lymph nodes

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 and Inflammation 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)
Immunodeficiency (specific T cell deficiency)
Immunodeficiency Associated with Other Defects

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

Virology Research
B and T Cell Deficiency

Genes & Alleles

Gene & Allele Information

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, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Cxcl10^tm1Adl related

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; 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]

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]

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]

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]

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]

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]

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as homozygotes.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000651 BALB/cJ
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.