Strain Name:

B6;129-Ncr1tm1Oman/J

Stock Number:

022739

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Availability:

Repository- Live

Common Names: B6.129-Ncr1tm1Oman/J;    
Ncr1gfp mice are useful when tracking natural killer cells during infection.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemWild-type x Heterozygote         (Female x Male)   25-OCT-13
Mating SystemHeterozygote x Wild-type         (Female x Male)   25-OCT-13
Specieslaboratory mouse
GenerationN10+pN1 (08-JAN-14)
Generation Definitions
 
Donating Investigator Ofer Mandelboim,   The Hebrew University of Jerusalem

Description
An internal ribosome entry site (IRES)-GFP (green fluorescent protein) fusion protein, replaces exons 5-7 of the natural cytotoxicity triggering receptor 1 (Ncr1 or NKp46), abolishing gene function. NCR1 is expressed specifically on natural killer (NK) cells and possibly on related innate lymphocytes. Homozygous mice are viable and fertile. These mice are more susceptible to influenza viral infection at the LD50 dose. The GFP reported reveals increased numbers of NK cells at sites of infection and decreased circulating NK cells during infection. This reporter also enables the identification of Interferon Producing Killer Dendritic Cells-like (IKDCs) as activated NK cells.

Development
A targeting vector was designed to replace exons 5-7 of the natural cytotoxicity triggering receptor 1 (Ncr1) with an internal ribosome entry site (IRES)-GFP (green fluorescent protein) fusion protein followed by a loxP-flanked neomycin (neo) resistance cassette. This construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-Kitl+-derived R1 embryonic stem (ES) cells. Chimeras were made by ES cell aggregation and chimeric mice were bred with C57BL/6-Tg(Zp3-cre)93Knw/J mice (Stock No. 003651) to delete the neo cassette. These Ncr1gfp mice were bred to C57BL/6 mice for at least 10 generations (see SNP note below). Upon arrival at The Jackson Laboratory Repository, mice were bred with C57BL/6J mice (Stock No. 000664) for at least one generation.

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. Three of the markers throughout the genome were still segregating for 129 suggesting an incomplete backcross.

Control Information

  Control
   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

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

Ncr1tm1Oman/Ncr1tm1Oman

        involves: 129S1/Sv * 129X1/SvJ
  • mortality/aging
  • increased susceptibility to viral infection induced morbidity/mortality
    • when infected with influenza A/PR8 virus, all homozygotes die within 9 days, compared to ~67% of wild-type and 58% of heterozygous littermates   (MGI Ref ID J:112394)
  • immune system phenotype
  • decreased NK cell number
    • 2 days after influenza infection, a marked reduction in NK cells in the blood is observed in mutants compared to wild-type; this correlates with increased percentages of NK cells in the lungs   (MGI Ref ID J:112394)
    • with time, numbers of NK cells in the blood increase to pre-infection levels while NK cells continue to increase in the lungs   (MGI Ref ID J:112394)
  • impaired natural killer cell mediated cytotoxicity
    • in vivo, killing of RMAS or RMA cells, both of which are NK cell-sensitive targets, is impaired compared to that in wild-type or heterozygotes; RMA cells are killed less efficiently than RMAS cells in mutants   (MGI Ref ID J:112394)
    • in vitro, splenocytes from mutants show little or no cytolytic activity against known NK cell target cell lines without activation by poly(I):poly(C) treatment   (MGI Ref ID J:112394)
  • increased susceptibility to viral infection induced morbidity/mortality
    • when infected with influenza A/PR8 virus, all homozygotes die within 9 days, compared to ~67% of wild-type and 58% of heterozygous littermates   (MGI Ref ID J:112394)
  • hematopoietic system phenotype
  • decreased NK cell number
    • 2 days after influenza infection, a marked reduction in NK cells in the blood is observed in mutants compared to wild-type; this correlates with increased percentages of NK cells in the lungs   (MGI Ref ID J:112394)
    • with time, numbers of NK cells in the blood increase to pre-infection levels while NK cells continue to increase in the lungs   (MGI Ref ID J:112394)
  • impaired natural killer cell mediated cytotoxicity
    • in vivo, killing of RMAS or RMA cells, both of which are NK cell-sensitive targets, is impaired compared to that in wild-type or heterozygotes; RMA cells are killed less efficiently than RMAS cells in mutants   (MGI Ref ID J:112394)
    • in vitro, splenocytes from mutants show little or no cytolytic activity against known NK cell target cell lines without activation by poly(I):poly(C) treatment   (MGI Ref ID J:112394)
View Research Applications

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

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      NK Cell Deficiency

Research Tools
Fluorescent Proteins
Genetics Research
      Tissue/Cell Markers
Immunology, Inflammation and Autoimmunity Research
      NK Cell Deficiency
      genes regulating susceptibility to infectious disease and endotoxin

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ncr1tm1Oman
Allele Name targeted mutation 1, Ofer Mandelboim
Allele Type Targeted (Reporter)
Common Name(s) Ncr1gfp;
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Site of ExpressionNcr1 is expressed specifically on natural killer (NK) cells and possibly on related innate lymphocytes.
Gene Symbol and Name Ncr1, natural cytotoxicity triggering receptor 1
Chromosome 7
Gene Common Name(s) CD335; KILR-1; LY94; Ly94; MAR1 (mouse activating receptor 1); NK-p46; NKP46; lymphocyte antigen 94;
Molecular Note A targeting vector was designed to replace exons 5-7 with an IRES-GFP-PGK-neo. The neo was removed via cre-mediated recombination. Absence of endogenous transcript was confirmed by RT-PCR. Fluorescence is more intense after excision by Tg(Prm-cre)58Og (129/Sv background) or by Tg(Sp3-cre)93Knw (C57BL/6 background). When allele is made congenic on 129 or C57BL/6 background, immune system phenotype is not altered by removal of PGK-neo or by background. [MGI Ref ID J:112394]

Genotyping

Genotyping Information

Genotyping Protocols

Ncr1tm1Oman, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Gazit R; Gruda R; Elboim M; Arnon TI; Katz G; Achdout H; Hanna J; Qimron U; Landau G; Greenbaum E; Zakay-Rones Z; Porgador A; Mandelboim O. 2006. Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1. Nat Immunol 7(5):517-23. [PubMed: 16565719]  [MGI Ref ID J:112394]

Additional References

Ncr1tm1Oman related

Beuneu H; Deguine J; Breart B; Mandelboim O; Di Santo JP; Bousso P. 2009. Dynamic behavior of NK cells during activation in lymph nodes. Blood 114(15):3227-34. [PubMed: 19667398]  [MGI Ref ID J:153545]

Chaushu S; Wilensky A; Gur C; Shapira L; Elboim M; Halftek G; Polak D; Achdout H; Bachrach G; Mandelboim O. 2012. Direct recognition of Fusobacterium nucleatum by the NK cell natural cytotoxicity receptor NKp46 aggravates periodontal disease. PLoS Pathog 8(3):e1002601. [PubMed: 22457623]  [MGI Ref ID J:195396]

Deguine J; Breart B; Lemaitre F; Bousso P. 2012. Cutting Edge: Tumor-Targeting Antibodies Enhance NKG2D-Mediated NK Cell Cytotoxicity by Stabilizing NK Cell-Tumor Cell Interactions. J Immunol 189(12):5493-7. [PubMed: 23183896]  [MGI Ref ID J:190837]

Deguine J; Breart B; Lemaitre F; Di Santo JP; Bousso P. 2010. Intravital Imaging Reveals Distinct Dynamics for Natural Killer and CD8(+) T Cells during Tumor Regression. Immunity 33(4):632-44. [PubMed: 20951068]  [MGI Ref ID J:165485]

Elboim M; Gazit R; Gur C; Ghadially H; Betser-Cohen G; Mandelboim O. 2010. Tumor immunoediting by NKp46. J Immunol 184(10):5637-44. [PubMed: 20404273]  [MGI Ref ID J:160984]

Elhaik-Goldman S; Kafka D; Yossef R; Hadad U; Elkabets M; Vallon-Eberhard A; Hulihel L; Jung S; Ghadially H; Braiman A; Apte RN; Mandelboim O; Dagan R; Mizrachi-Nebenzahl Y; Porgador A. 2011. The Natural Cytotoxicity Receptor 1 Contribution to Early Clearance of Streptococcus pneumoniae and to Natural Killer-Macrophage Cross Talk. PLoS One 6(8):e23472. [PubMed: 21887255]  [MGI Ref ID J:176154]

Garcia Z; Lemaitre F; van Rooijen N; Albert ML; Levy Y; Schwartz O; Bousso P. 2012. Subcapsular sinus macrophages promote NK cell accumulation and activation in response to lymph-borne viral particles. Blood 120(24):4744-50. [PubMed: 23065157]  [MGI Ref ID J:192366]

Ghadially H; Horani A; Glasner A; Elboim M; Gazit R; Shoseyov D; Mandelboim O. 2013. NKp46 regulates allergic responses. Eur J Immunol 43(11):3006-16. [PubMed: 23878025]  [MGI Ref ID J:203010]

Glasner A; Ghadially H; Gur C; Stanietsky N; Tsukerman P; Enk J; Mandelboim O. 2012. Recognition and Prevention of Tumor Metastasis by the NK Receptor NKp46/NCR1. J Immunol 188(6):2509-15. [PubMed: 22308311]  [MGI Ref ID J:181865]

Grin'kina NM; Karnabi EE; Damania D; Wadgaonkar S; Muslimov IA; Wadgaonkar R. 2012. Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation. PLoS One 7(5):e36475. [PubMed: 22615770]  [MGI Ref ID J:187238]

Gur C; Porgador A; Elboim M; Gazit R; Mizrahi S; Stern-Ginossar N; Achdout H; Ghadially H; Dor Y; Nir T; Doviner V; Hershkovitz O; Mendelson M; Naparstek Y; Mandelboim O. 2010. The activating receptor NKp46 is essential for the development of type 1 diabetes. Nat Immunol 11(2):121-8. [PubMed: 20023661]  [MGI Ref ID J:158411]

Halfteck GG; Elboim M; Gur C; Achdout H; Ghadially H; Mandelboim O. 2009. Enhanced in vivo growth of lymphoma tumors in the absence of the NK-activating receptor NKp46/NCR1. J Immunol 182(4):2221-30. [PubMed: 19201876]  [MGI Ref ID J:144790]

Satoh-Takayama N; Dumoutier L; Lesjean-Pottier S; Ribeiro VS; Mandelboim O; Renauld JC; Vosshenrich CA; Di Santo JP. 2009. The natural cytotoxicity receptor NKp46 is dispensable for IL-22-mediated innate intestinal immune defense against Citrobacter rodentium. J Immunol 183(10):6579-87. [PubMed: 19846871]  [MGI Ref ID J:157183]

Satoh-Takayama N; Lesjean-Pottier S; Vieira P; Sawa S; Eberl G; Vosshenrich CA; Di Santo JP. 2010. IL-7 and IL-15 independently program the differentiation of intestinal CD3-NKp46+ cell subsets from Id2-dependent precursors. J Exp Med 207(2):273-80. [PubMed: 20142427]  [MGI Ref ID J:158828]

Satoh-Takayama N; Vosshenrich CA; Lesjean-Pottier S; Sawa S; Lochner M; Rattis F; Mention JJ; Thiam K; Cerf-Bensussan N; Mandelboim O; Eberl G; Di Santo JP. 2008. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29(6):958-70. [PubMed: 19084435]  [MGI Ref ID J:142654]

Sheppard S; Triulzi C; Ardolino M; Serna D; Zhang L; Raulet DH; Guerra N. 2013. Characterization of a novel NKG2D and NKp46 double-mutant mouse reveals subtle variations in the NK cell repertoire. Blood 121(25):5025-33. [PubMed: 23649470]  [MGI Ref ID J:198931]

Vosshenrich CA; Lesjean-Pottier S; Hasan M; Richard-Le Goff O; Corcuff E; Mandelboim O; Di Santo JP. 2007. CD11cloB220+ interferon-producing killer dendritic cells are activated natural killer cells. J Exp Med 204(11):2569-78. [PubMed: 17923507]  [MGI Ref ID J:126100]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony, or to C57BL/6J inbred mice (Stock No. 000664).
Mating SystemWild-type x Heterozygote         (Female x Male)   25-OCT-13
Heterozygote x Wild-type         (Female x Male)   25-OCT-13

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 $232.00Female or MaleHeterozygous for Ncr1tm1Oman  
Price per Pair (US dollars $)Pair Genotype
$302.00Heterozygous for Ncr1tm1Oman x Wild-type for Ncr1tm1Oman  
$302.00Wild-type for Ncr1tm1Oman x Heterozygous for Ncr1tm1Oman  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHeterozygous for Ncr1tm1Oman  
Price per Pair (US dollars $)Pair Genotype
$392.60Heterozygous for Ncr1tm1Oman x Wild-type for Ncr1tm1Oman  
$392.60Wild-type for Ncr1tm1Oman x Heterozygous for Ncr1tm1Oman  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.

Control Information

  Control
   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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