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- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
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Description
Strain Information
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Homozygote x Homozygote (Female x Male) 20-OCT-09 Species laboratory mouse Generation N6+N4F4 (19-FEB-09) Donating Investigator Richard Lang, Cincinnati Children's Hospital Description
These 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. Mice that are homozygous for the transgene are viable, normal in size and do not display any gross physical or behavioral abnormalities. Transgene expression is not sufficient to be detected by FACS analysis. 12 hours following DT administration all macrophages are ablated in the peritoneum, kidney and ovary. Macrophage population is restored by day 4 following a single intraperitoneal dose of DT. Administration of DT does not affect polymorphonuclear cells. Higher doses (greater than 25ng/g body weight) of DT sickens the mice. This mutant mouse strain may be useful in studies of the specific role of macrophages in the immune response.In an attempt to offer alleles 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. 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 transgenic construct containing sequence encoding DTR/GFP under the control of the human ITGAM (integrin alpha M) promoter was introduced into fertilized FVB/N donor eggs. Founder line 34 was subsequently established. The mice were backcrossed onto C57BL/6 for 6 generations (January 2006).
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Fluorescent Protein Strains
View Fluorescent Protein Strains (225 strains)
005515 FVB-Tg(ITGAM-DTR/EGFP)34Lan/J 008547 NOD.FVB-Tg(ITGAM-DTR/EGFP)34Lan/JdkJ
004509 B6.FVB-Tg(Itgax-DTR/EGFP)57Lan/J 004512 C.FVB-Tg(Itgax-DTR/EGFP)57Lan/J 008549 NOD.FVB-Tg(Itgax-DTR/EGFP)57Lan/JdkJ
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(ITGAM-DTR/EGFP)34Lan/0
involves: FVB/N
- immune system phenotype
- abnormal macrophage morphology (MGI Ref ID J:95141)
- bone marrow derived macrophages express human diphtheria toxin receptor
- decreased macrophage cell number (MGI Ref ID J:95141)
- 24 hours after one injection of diphtheria toxin, peritoneal macrophages and blood monocytes are reduced by 4-fold
- peritoneal macrophages are eliminated after two injections of diphtheria toxin
- scar associated macrophages found in mouse model of hepatic fibrosis are significantly reduced after diphtheria toxin treatment
- increased neutrophil cell number (MGI Ref ID J:95141)
- the number of neutrophils isolated from the peritoneum is doubled 24 hours after injection with diphtheria toxin
- homeostasis/metabolism phenotype
- decreased susceptibility to injury (MGI Ref ID J:131371)
- following administration of diphtheria toxin, mice exhibit less renal fibrosis following unilateral ureter obstruction compared to wild-type mice
- renal/urinary system phenotype
- abnormal kidney physiology (MGI Ref ID J:131371)
- following administration of diphtheria toxin, mice exhibit less renal fibrosis following unilateral ureter obstruction compared to wild-type mice
- liver/biliary system phenotype
- liver fibrosis (MGI Ref ID J:95141)
- fibrosis induced by chemical injury has less elastin, collagen III and other collagen components associated with it when mice are depleted of macrophages by diphtheria toxin
- there is also a reduction in activated hepatic stellate cells associated with the liver injuries
- there is a reduced number of proliferating and apoptotic cells associated with the scars induced by chemical injury in mice depleted of macrophages
- when macrophages are depleted during the recovery phase of the hepatic fibrosis model, there is very little attenuation in perisinusoidal fibrosis
- hematopoietic system phenotype
- abnormal macrophage morphology (MGI Ref ID J:95141)
- bone marrow derived macrophages express human diphtheria toxin receptor
- decreased macrophage cell number (MGI Ref ID J:95141)
- 24 hours after one injection of diphtheria toxin, peritoneal macrophages and blood monocytes are reduced by 4-fold
- peritoneal macrophages are eliminated after two injections of diphtheria toxin
- scar associated macrophages found in mouse model of hepatic fibrosis are significantly reduced after diphtheria toxin treatment
- increased neutrophil cell number (MGI Ref ID J:95141)
- the number of neutrophils isolated from the peritoneum is doubled 24 hours after injection with diphtheria toxin
This mouse can be used to support research in many areas including:
GFP relatedResearch Tools
Cell Biology Research
Fluorescent Proteins
Hematological Research
Immunology and Inflammation Research
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(ITGAM-DTR/EGFP)34Lan | ||
|---|---|---|---|
| Allele Name | transgene insertion 34, Richard A Lang | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | CD11b-DTR; tg(CD11b-DTR)Llan; | ||
| Mutation Made By | Richard Lang, Cincinnati Children's Hospital | ||
| Strain of Origin | FVB/N | ||
| Site of Expression | Induced in monocytes/macrophages (fluorescence not sufficient for FACS); transient diptheria toxin (DT)-induced ablation of cells. | ||
| 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. | |||
| Expressed Gene | DTR, Simian Diphtheria Toxin Receptor, | ||
| Promoter | ITGAM, integrin, alpha M (complement component 3 receptor 3 subunit), human | ||
| 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. [MGI Ref ID J:95141] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Fluorescent Proteins (Generic GFP), Melt Curve Analysis
Fluorescent Proteins -- Generic GFP, QPCR
TG(DTR/EGFP), Standard PCR
Tg(ITGAM-DTR/EGFP), Melt Curve Analysis
Helpful Links
Genotyping resources and troubleshooting
References
References
Selected Reference(s)
Duffield JS; Forbes SJ; Constandinou CM; Clay S; Partolina M; Vuthoori S; Wu S; Lang R; Iredale JP. 2005. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 115(1):56-65. [PubMed: 15630444] [MGI Ref ID J:95141]
Additional References
Tg(ITGAM-DTR/EGFP)34Lan relatedAhn GO; Brown JM. 2008. Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Cancer Cell 13(3):193-205. [PubMed: 18328424] [MGI Ref ID J:132946]
Arnold L; Henry A; Poron F; Baba-Amer Y; van Rooijen N; Plonquet A; Gherardi RK; Chazaud B. 2007. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 204(5):1057-69. [PubMed: 17485518] [MGI Ref ID J:125715]
Cailhier JF; Sawatzky DA; Kipari T; Houlberg K; Walbaum D; Watson S; Lang RA; Clay S; Kluth D; Savill J; Hughes J. 2006. Resident pleural macrophages are key orchestrators of neutrophil recruitment in pleural inflammation. Am J Respir Crit Care Med 173(5):540-7. [PubMed: 16357332] [MGI Ref ID J:128684]
Fallowfield JA; Mizuno M; Kendall TJ; Constandinou CM; Benyon RC; Duffield JS; Iredale JP. 2007. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J Immunol 178(8):5288-95. [PubMed: 17404313] [MGI Ref ID J:145269]
Henderson NC; Mackinnon AC; Farnworth SL; Kipari T; Haslett C; Iredale JP; Liu FT; Hughes J; Sethi T. 2008. Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis. Am J Pathol 172(2):288-98. [PubMed: 18202187] [MGI Ref ID J:131371]
Qian B; Deng Y; Im JH; Muschel RJ; Zou Y; Li J; Lang RA; Pollard JW. 2009. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One 4(8):e6562. [PubMed: 19668347] [MGI Ref ID J:152473]
Saxena V; Ondr JK; Magnusen AF; Munn DH; Katz JD. 2007. The countervailing actions of myeloid and plasmacytoid dendritic cells control autoimmune diabetes in the nonobese diabetic mouse. J Immunol 179(8):5041-53. [PubMed: 17911589] [MGI Ref ID J:137009]
Sokol CL; Chu NQ; Yu S; Nish SA; Laufer TM; Medzhitov R. 2009. Basophils function as antigen-presenting cells for an allergen-induced T helper type 2 response. Nat Immunol 10(7):713-20. [PubMed: 19465907] [MGI Ref ID J:150141]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred together. If generated, homozygous offspring may also be bred together (although the phenotype of such animals is not currently known [Sep-2006]). Mating System Homozygote x Homozygote (Female x Male) 20-OCT-09 Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $209.90 Female or Male Homozygous for Tg(ITGAM-DTR/EGFP)34Lan
Pairs /Price (US dollars $) Pair Genotype $419.80 Homozygous for Tg(ITGAM-DTR/EGFP)34Lan x Homozygous for Tg(ITGAM-DTR/EGFP)34Lan
Additional Supply Details
| Pricing for International shipping destinations |
|
Weeks of Age Price (US dollars $) Gender Genotypes Provided Individual Mouse $272.90 Female or Male Homozygous for Tg(ITGAM-DTR/EGFP)34Lan
Pairs /Price (US dollars $) Pair Genotype $545.80 Homozygous for Tg(ITGAM-DTR/EGFP)34Lan x Homozygous for Tg(ITGAM-DTR/EGFP)34Lan
Additional Supply Details
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| 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. | ||
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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 and Purchasing Information
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