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| These Macrophage Fas-Induced Apoptosis (MAFIA) transgenic mice allow inducible/reversible apoptosis of macrophages and dendritic cells. This Fas suicide/apoptotic system uses the mouse colony stimulating factor 1 receptor promoter (Csf1r) to drive expression of a mutant human FK506 binding protein 1A, 12kDa (FKBP12). When FKBP12 binds the dimerization drug AP20187, macrophages and dendritic cells undergo apoptosis. Cessation of AP20187 treatment permits those cell populations to rebound. The transgene also allows fluorescent labeling of Csf1r-expressing cells. | |||||||||||||||||||
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Description
Strain Information
Former Names C57BL/6J-Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck/J (Changed: 11-AUG-06 ) C57BL/6J-Tg(Csf1r-GFP, NGFR/FKBP12)2Bck/J (Changed: 15-DEC-04 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Species laboratory mouse Generation N6F?+N1F16 (24-MAR-11)
Generation DefinitionsDonating Investigator Donald Cohen, University of Kentucky Description
These Macrophage Fas-Induced Apoptosis (MAFIA) transgenic mice have an inducible Fas suicide/ apoptotic system driven by the mouse Csf1r, colony stimulating factor 1 receptor promoter. The transgene insert contains a mutant human FK506 binding protein 1A, 12kDa (FKBP12) which preferentially binds the dimerization drug AP20187. Enhanced Green Fluorescent Protein (EGFP) fluorescence and transgene expression is detected in 78% of isolated peritoneal cells. EGFP fluorescence is variable among tissues (B- and T-cells do not express EGFP). Administration of the dimerizing reagent, AP20187, induces apoptosis in macrophages and dendritic cells (intravenous injection of dimerizer is recommended, since the intraperitoneal route can elicit peritoneal adhesions). In treated mice, EGFP fluorescing peritoneal and bone marrow macrophage numbers are depleted by more than 90%, and macrophage numbers in blood, spleen, lung and thymus by more than 70%. 7 days after cessation of treatment, the EGFP fluorescing macrophage and dendritic cell populations rebound. Homozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This strain may contain multiple transgene insertion sites, and as such, the donating investigator recommends that all offspring be screened for EGFP expression (via flow cytometry).Development
An FKBP-Fas suicide construct (containing an IRES sequence, human low affinity nerve growth factor receptor [deltaLNGFR], 2 copies of the 12kDa human FK506 binding protein 1A [FKBP12], and the intracellular domain region of the Fas gene) was inserted immediately downstream of the Enhanced Green Fluorescent Protein (EGFP, Clonetech) gene. This entire construct was placed under the control of the mouse colony stimulating factor 1 receptor (Csf1r) promoter. The resulting 11.1 kb transgene (termed Macrophage Fas-Induced Apoptosis or MaFIA) was introduced into C57BL/6 donor eggs. The resulting male transgenic mice (founder line 2) were bred to C57BL/6 mice for 6 generations prior to arrival at The Jackson Laboratory.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, 2 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 | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
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Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck/Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck
C57BL/6
- normal phenotype
- no abnormal phenotype detected
- mice homozygous for the transgene are viable and exhibit no gross physical or behavioral abnormalities (MGI Ref ID J:89035)
This mouse can be used to support research in many areas including:
GFP relatedImmunology and Inflammation Research
Immunodeficiency
Macrophage defects
Research Tools
Apoptosis Research
Cell Biology Research
Fluorescent Proteins
Genetics Research
Tissue/Cell Markers
Hematological Research
Immunology and Inflammation Research
Macrophage Deficiency
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck | ||
|---|---|---|---|
| Allele Name | transgene insertion 2, Donald A Cohen | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | MaFIA (Macrophage Fas-Induced Apoptosis); Mafia; | ||
| Mutation Made By | Sandra Hale-Burnett, Brigham Young University | ||
| Strain of Origin | C57BL/6 | ||
| Site of Expression | Expression of GFP and the NGFR/FKBP12 transgene is detected in 78% of isolated peritoneal cells. GFP expression is variable among tissues. B and T cells do not express GFP. Administration of AP20187 induces apoptosis inmacrophages and dendritic cells. | ||
| Expressed Gene | NGFR, nerve growth factor receptor, human | ||
| Expressed Gene | TNFRSF6B, tumor necrosis factor receptor superfamily, member 6b, decoy, human | ||
| Expressed Gene | FKBP1A, FK506 binding protein 1A, 12kDa, human | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Promoter | Csf1r, colony stimulating factor 1 receptor, mouse, laboratory | ||
| General Note |
Homozygous mutant mice are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities. The transgene is expressed constitutively in macrophages and dendritic cells and permits conditional ablation of these cellpopulations in the mouse. Oligomerization of the fusion protein by binding of a bivalent FK506 analog causes them to undergo apoptosis via the Fas-mediated pathway. In transgenic mice treated with the dimerizing reagent AP20187, EGFP fluorescing peritoneal and bone marrow macrophage numbers are depleted by more than 90%, and macrophage numbers in blood, spleen, lung and thymus by more than 70%. Seven days after cessation of treatment, the EGFP fluorescing macrophage and dendritic cell populations rebound. | ||
| Molecular Note | The transgene's bicistronic transcript, expressed from the promoter of the macrophage-expressed colony stimulating factor 1 receptor gene, encodes enhanced green fluorescent protein (EGFP) and a conditionally apoptotic fusion protein. The latter comprises the extracellular and transmembrane domains of the human low affinity nerve growth factor receptor, two tandem copies of the human FK506 binding protein, and the intracellular domain of human TNFRSF6 - the Fas receptor protein - and is translated from an internal RNA expression signal (IRES) inserted at the translation start codon of the nerve growth factor receptor (NGFR) coding sequence. [MGI Ref ID J:89035] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), Melt Curve Analysis
Fluorescent Proteins (Generic GFP), Standard PCR
Fluorescent Proteins -- Generic GFP, QPCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Burnett SH; Kershen EJ; Zhang J; Zeng L; Straley SC; Kaplan AM; Cohen DA. 2004. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J Leukoc Biol 75(4):612-23. [PubMed: 14726498] [MGI Ref ID J:89035]
Additional References
Luther SA; Lopez T; Bai W; Hanahan D; Cyster JG. 2000. BLC expression in pancreatic islets causes B cell recruitment and lymphotoxin-dependent lymphoid neogenesis. Immunity 12(5):471-81. [PubMed: 10843380] [MGI Ref ID J:110548]
Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck relatedAikawa Y; Katsumoto T; Zhang P; Shima H; Shino M; Terui K; Ito E; Ohno H; Stanley ER; Singh H; Tenen DG; Kitabayashi I. 2010. PU.1-mediated upregulation of CSF1R is crucial for leukemia stem cell potential induced by MOZ-TIF2. Nat Med 16(5):580-5, 1p following 585. [PubMed: 20418886] [MGI Ref ID J:161535]
Bogunovic M; Ginhoux F; Helft J; Shang L; Hashimoto D; Greter M; Liu K; Jakubzick C; Ingersoll MA; Leboeuf M; Stanley ER; Nussenzweig M; Lira SA; Randolph GJ; Merad M. 2009. Origin of the lamina propria dendritic cell network. Immunity 31(3):513-25. [PubMed: 19733489] [MGI Ref ID J:152688]
Chow A; Lucas D; Hidalgo A; Mendez-Ferrer S; Hashimoto D; Scheiermann C; Battista M; Leboeuf M; Prophete C; van Rooijen N; Tanaka M; Merad M; Frenette PS. 2011. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 208(2):261-71. [PubMed: 21282381] [MGI Ref ID J:176846]
Ginhoux F; Liu K; Helft J; Bogunovic M; Greter M; Hashimoto D; Price J; Yin N; Bromberg J; Lira SA; Stanley ER; Nussenzweig M; Merad M. 2009. The origin and development of nonlymphoid tissue CD103+ DCs. J Exp Med 206(13):3115-30. [PubMed: 20008528] [MGI Ref ID J:155668]
Ishii M; Egen JG; Klauschen F; Meier-Schellersheim M; Saeki Y; Vacher J; Proia RL; Germain RN. 2009. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature 458(7237):524-8. [PubMed: 19204730] [MGI Ref ID J:147106]
Leal SM Jr; Cowden S; Hsia YC; Ghannoum MA; Momany M; Pearlman E. 2010. Distinct roles for Dectin-1 and TLR4 in the pathogenesis of Aspergillus fumigatus keratitis. PLoS Pathog 6:e1000976. [PubMed: 20617171] [MGI Ref ID J:162398]
Lindauer ML; Wong J; Iwakura Y; Magun BE. 2009. Pulmonary inflammation triggered by ricin toxin requires macrophages and IL-1 signaling. J Immunol 183(2):1419-26. [PubMed: 19561099] [MGI Ref ID J:151660]
Ma G; Pan PY; Eisenstein S; Divino CM; Lowell CA; Takai T; Chen SH. 2011. Paired Immunoglobin-like Receptor-B Regulates the Suppressive Function and Fate of Myeloid-Derived Suppressor Cells. Immunity 34(3):385-95. [PubMed: 21376641] [MGI Ref ID J:170325]
Markey KA; Banovic T; Kuns RD; Olver SD; Don AL; Raffelt NC; Wilson YA; Raggatt LJ; Pettit AR; Bromberg JS; Hill GR; MacDonald KP. 2009. Conventional dendritic cells are the critical donor APC presenting alloantigen after experimental bone marrow transplantation. Blood 113(22):5644-9. [PubMed: 19336758] [MGI Ref ID J:148895]
Pan PY; Ma G; Weber KJ; Ozao-Choy J; Wang G; Yin B; Divino CM; Chen SH. 2010. Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res 70(1):99-108. [PubMed: 19996287] [MGI Ref ID J:155743]
Qualls JE; Kaplan AM; van Rooijen N; Cohen DA. 2006. Suppression of experimental colitis by intestinal mononuclear phagocytes. J Leukoc Biol 80(4):802-15. [PubMed: 16888083] [MGI Ref ID J:113033]
Soderquest K; Powell N; Luci C; van Rooijen N; Hidalgo A; Geissmann F; Walzer T; Lord GM; Martin-Fontecha A. 2011. Monocytes control natural killer cell differentiation to effector phenotypes. Blood 117(17):4511-8. [PubMed: 21389319] [MGI Ref ID J:172809]
Sun K; Gan Y; Metzger DW. 2011. Analysis of murine genetic predisposition to pneumococcal infection reveals a critical role of alveolar macrophages in maintaining the sterility of the lower respiratory tract. Infect Immun 79(5):1842-7. [PubMed: 21321074] [MGI Ref ID J:171962]
Sun Y; Karmakar M; Roy S; Ramadan RT; Williams SR; Howell S; Shive CL; Han Y; Stopford CM; Rietsch A; Pearlman E. 2010. TLR4 and TLR5 on corneal macrophages regulate Pseudomonas aeruginosa keratitis by signaling through MyD88-dependent and -independent pathways. J Immunol 185(7):4272-83. [PubMed: 20826748] [MGI Ref ID J:164286]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, transgenic mice can be bred together, to wildtype siblings, or to C57BL/6J wildtype mice. Mating System Homozygote x Homozygote (Female x Male) 01-MAR-06 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $140.00 Female or Male Homozygous for Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck
Pairs /Price (US dollars $) Pair Genotype $280.00 Homozygous for Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck x Homozygous for Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order 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.
| Pricing for International shipping destinations |
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Live Mice
Price (US dollars $) Gender Genotypes Provided Individual Mouse $182.00 Female or Male Homozygous for Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck
Pairs /Price (US dollars $) Pair Genotype $364.00 Homozygous for Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck x Homozygous for Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order 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.
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Standard Supply
Repository-Live. The Repository Strains represent an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. We treat orders for these strains as custom orders. Within 2 business days, we respond to each availability inquiry or order 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.
General Supply Notes
- This strain is included in the Induced Mutant Resource Colony collection.
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| 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.Ordering Information
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For Licensing and Use Restrictions view the link(s) below:
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