| Allele Name | transgene insertion 2, Donald A Cohen |
| Allele Type | Transgenic (Reporter, Inserted expressed sequence, Humanized sequence) |
| Allele Synonym(s) | Mafia; MaFIA (Macrophage Fas-Induced Apoptosis); Tg(Csf1r-GFP, NGFR/FKBP12)2Bck |
| Gene Symbol and Name | Tg(Csf1r-EGFP-NGFR/FKBP1A/TNFRSF6)2Bck, transgene insertion 2, Donald A Cohen |
| Gene Synonym(s) | |
| Promoter | Csf1r, colony stimulating factor 1 receptor, mouse, laboratory |
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| Expressed Gene | NGFR, nerve growth factor receptor, human |
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| Expressed Gene | TNFRSF6B, TNF receptor superfamily member 6b, human |
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| Expressed Gene | FKBP1A, FK506 binding protein 1A, human |
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| Expressed Gene | GFP, Green Fluorescent Protein, |
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| 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. |
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| Strain of Origin | C57BL/6 |
| Chromosome | UN |
| 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 cell populations 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. |
| Mutations Made By | Sandra Hale-Burnett, Brigham Young University |
