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

Stock number: 004512
Product name: CD11c-DTR
Research areas: 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. CD11c-DTR/GFP transgenic mice are useful in studies of mononuclear phagocyte origins and the specific role of dendritic cells in the immune response.

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]).
Mice that are homozygous for the transgene are viable, normal in size and do not display any gross physical or behavioral abnormalities. Upon diphtheria toxin (DT) administration, mice harboring this transgene are transiently depleted of dendritic cell (DC) populations. All CD8⁺ and CD8^- DC in the spleen express EGFP and are DT sensitive. 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 is lethal to the mouse. Long term depletion of this cell population can be achieved by the generation of mixed irradiation chimeras.
CD11c-DTR/GFP transgenic mice are useful in studies of mononuclear phagocyte origins and the specific role of dendritic cells 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

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. The resulting chimeric animals were crossed to BALB/c mice. Founder line 57 was then backcrossed to BALB/c for eight generations (May 2006).
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.