These congenic NOD mice are hemizygous for a transgene encoding a simian diphtheria toxin receptor fused with green fluorescent protein under the control of human integrin alpha M, ITGAM, promoter (CD11b). These transgenic mice provide a diphtheria toxin inducible system that transiently depletes macrophages. This transgenic strain is useful for studying the specific role of macrophages in the immune response, specifically in the context of type 1 diabetes.
Jonathan D Katz, Cincinnati Children's Research Foundatio
Genetic Background | Generation |
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001976 NOD/ShiLtJ |
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Allele Type |
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Transgenic (Inserted expressed sequence) |
Transgenic mice have a diphtheria toxin (DT) inducible system that transiently depletes macrophages. The transgene insert contains a fusion product involving simian diphtheria toxin receptor and green fluorescent protein under the control of the human ITGAM (integrin alpha M) promoter (CD11b). RT-PCR analysis of bone marrow macrophages detects specific transgene expression. Cytological analysis of thioglycollate treated peritoneal cells shows the absence of macrophages. Intraperitoneal injection of DT ablates monocyte/macrophage cells in the peritoneal cavity. Unmanipulated CD11b/DTR NOD mice are viable, normal in size and develop spontaneous diabetes similar to NOD/ShiLtJ. Transgene expression of EGFP is not sufficient to be detected by FACS analysis. Twelve hours following DT administration all macrophages are ablated in the spleen and lymph nodes, including the pancreatic lymph node and pancreas for three to five days. Macrophage population is restored by day four following a single intraperitoneal dose of DT. Administration of DT does not affect polymorphonuclear cells. DT treated CD11b-DTR/NOD.scid mice and controls used in diabetes transfer studies became diabetic by days 10-14. Higher doses (greater than 25ng/g body weight) of DT sickens the mice. Transgene expression is not sufficient to be detected by FACS analysis. This mutant mouse strain may be useful in studies of the specific role of macrophages in the immune response, specifically in the context of type 1 diabetes.
A transgenic construct containing sequence encoding simian Diphtheria Toxin Receptor (DTR)-Enhanced Green Fluorescent Protein (EGFP) fusion protein under the control of human integrin, alpha M (complement component 3 receptor 3 subunit), ITGAM, promoter was introduced into fertilized FVB/N donor eggs. Progeny of founder line 34 were crossed to NOD/ShiLt mice. In 2008, the Type 1 Diabetes Resource received this transgenic NOD congeic strain at generation N22 and mated to NOD/ShiLtJ (Stock No. 001976) for one generation prior to sibling mating.
Expressed Gene | DTR, Simian Diphtheria Toxin Receptor, |
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Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | Induced in monocytes/macrophages (fluorescence not sufficient for FACS); transient diptheria toxin (DT)-induced ablation of cells. |
Allele Name | transgene insertion 34, Richard A Lang |
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Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | CD11b-DTR; tg(CD11b-DTR)Llan |
Gene Symbol and Name | Tg(ITGAM-DTR/EGFP)34Lan, transgene insertion 34, Richard A Lang |
Gene Synonym(s) | |
Promoter | ITGAM, integrin subunit alpha M, human |
Expressed Gene | DTR, Simian Diphtheria Toxin Receptor, |
Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | Induced in monocytes/macrophages (fluorescence not sufficient for FACS); transient diptheria toxin (DT)-induced ablation of cells. |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | The transgene contains a fusion product involving simian diphtheria toxin receptor and green fluorescent protein under the control of the human ITGAM (integrin alpha M) promoter (CD11b), and human growth hormone sequence. Mice carrying this transgene have a diphtheria toxin (DT) inducible system that transiently depletes macrophages. RT-PCR analysis of bone marrow macrophages detects specific transgene expression. |
Mutations Made By | Richard Lang, Cincinnati Children's Hospital |
When using the NOD.CD11b-DTR mouse strain in a publication, please cite the originating article(s) and include JAX stock #008547 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous or non-carrier for Tg(ITGAM-DTR/EGFP)34Lan |
Frozen Mouse Embryo | NOD.FVB-Tg(ITGAM-DTR/EGFP)34Lan/JdkJ | $2595.00 |
Frozen Mouse Embryo | NOD.FVB-Tg(ITGAM-DTR/EGFP)34Lan/JdkJ | $2595.00 |
Frozen Mouse Embryo | NOD.FVB-Tg(ITGAM-DTR/EGFP)34Lan/JdkJ | $3373.50 |
Frozen Mouse Embryo | NOD.FVB-Tg(ITGAM-DTR/EGFP)34Lan/JdkJ | $3373.50 |
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