NOD.FVB-1700016L21Rik^{Tg(Itgax-DTR/EGFP)57Lan}/JdkJ

Stock number: 008549
Product name: CD11c-DTR/NOD
Strain synonyms: NOD.CD11c-DTR
Research areas: Diabetes and Obesity Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

CD11c-DTR/GFP transgenic line 57 has the CD11c promoter (Itgax) directing expression of a diphtheria toxin receptor - enhanced green fluorescent protein (DTR/EGFP) fusion protein to dendritic cell populations. Administration of diphtheria toxin results in depletion of dendritic cell populations. NOD-congenic CD11c-DTR/GFP transgenic mice are useful in studies of mononuclear phagocyte origins and the specific role of dendritic cells in the immune response, specifically type 1 diabetes.

In Goodwin et al. 2019 Genome Res. 29:494, it was discovered that line 57 has more than 20 copies of the CD11c-DTR/GFP transgene inserted into the 1700016L21Rik locus on chromosome 1 (80448681-80455738 bp [Build GRCm38/mm10]).

Detailed description

CD11c-DTR/GFP transgenic line 57 has the CD11c promoter (Itgax) directing expression of a diphtheria toxin receptor - enhanced green fluorescent protein (DTR/EGFP) fusion protein to dendritic cell populations. Line 57 has more than 20 copies of the CD11c-DTR/GFP transgene inserted into the 1700016L21Rik locus on chromosome 1 (80448681-80455738 bp [Build GRCm38/mm10]).
Unmanipulated NOD congenic Itgax-DTR/EGFP (Cd11c-DTR) transgenic mice are viable, normal in size and develop spontaneous diabetes similar to NOD/ShiLtJ. All splenic CD8⁺ and CD8^- DC express EGFP and are diphtheria toxin (DT) sensitive. Upon DT administration, mice harboring this transgene are transiently depleted of dendritic cell (DC) populations. Immunohistochemical and flow cytometric analysis reveals EGFP expression and DT-inducible depletion of CD11c^high DC in spleen, lymph node, lung, liver and lamina propria tissues, as well as the defined macrophage subpopulations of the alveolar, lamina propria, metallophillic and marginal zone. Rapid reduction of CD11c⁺ DC populations induced by intraperitoneal injection of DT persists for approximately 2 days, after which the cell population gradually recovers. While transient DC depletion was not associated with sign of illness or long-term defects, repeated DT induction induces an acute spike in the production of IFN-gamma and TNF-alpha and is lethal to the mouse. Long term depletion of this cell population without toxicity can be achieved by the generation of mixed irradiation chimeras. Irradiated NOD mice reconstituted with CD11c-DTR bone marrow treated long term with DT to ablate DC failed to develop insulitis.
CD11c-DTR/GFP transgenic mice are useful in studies of the specific role of dendritic cells in the immune response, specifically type 1 diabetes.

Development

The CD11c-DTR/GFP transgene was designed to place a simian Diphtheria Toxin Receptor (DTR)-Enhanced Green Fluorescent Protein (EGFP, Stratagene) fusion protein under the control of the Itgax (or CD11c) promoter. This transgene was introduced into fertilized FVB/N donor eggs. Progeny of founder 57 were backcrossed to NOD/ShiLtJ for more than 10 generations. In 2008, the Type 1 Diabetes Resource received this transgenic NOD congeic strain and mated to NOD/ShiLtJ (Stock No. 001976) for one generation prior to sibling mating.
In 2008, single nucleotide polymorphism (SNP) analysis by The Jackson Laboratory estimated CD11c-DTR/GFP transgenic line 57 had an integration site on chromosome 1 (~52 cM). In 2017, more detailed analysis of the C57BL/6-congenic CD11c-DTR/GFP line 57 (Stock No. 004509) identified line 57 has more than 20 copies of the CD11c-DTR/GFP transgene inserted into the 1700016L21Rik locus on chromosome 1 (80448681-80455738 bp [Build GRCm38/mm10]).

Allele

Symbol: 1700016L21Rik^{Tg(Itgax-DTR/EGFP)57Lan}
Name: transgene insertion 57, Richard A Lang
MGI accession ID: MGI:3057163
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: 1700016L21Rik
Marker name: RIKEN cDNA 1700016L21 gene
Chromosome: 1
Strain of origin: FVB/N
Expressed genes: GFP,Green Fluorescent Protein,; DTR,Simian Diphtheria Toxin Receptor,
Site of expression: Expression of the transgene is specific to splenic dendritic cells. All CD8+ and CD8- dentritic cells in the spleen fluoresce and are DT sensititve.
Molecular note: The transgene contains a fusion product involving simian diphtheria toxin receptor and green fluorescent protein under the control of the mouse Itgax promoter (CD11c). Two lines were created (line 11 and line 57) with 1 to 2 copies and 20 copies of the transgene, respectively. All CD8+ and CD8- dendritic cells in the spleen fluoresce and are DT sensitive. Immunohistochemical and flow cytometric analyses show that expression of the transgene is specific to splenic dendritic cells. Line 57 inserted into the gene at 80448681-80455738 (Build GRCm38/mm10) resulting in a 7057 bp deletion. Founder line 57 has a copy number of greater than 20.