These CD11c-dnTGFbRIII transgenic mice express a dominant negative form of the human transforming growth factor, beta receptor II gene under the control of a CD11c (Itgax) promoter. Expression of the transgene is detected by RT-PCR in CD11c-expressing cells, including natural killer (NK) cell and lymphoid/myeloid dendritic cell (DC) subsets. Expression is not detected in natural killer T cells (NKT) cells, T cells or B cells isolated from transgenic mice. Transgenic mice show a selective dysregulation of NK cell homeostasis due to a blockage of transforming growth factor, beta (Tgfb) signalling. Large numbers of NK cells capable of producing considerable levels of interferon gamma (IFN-g) lead to downstream T helper type 1 (TH1) cell polarization.
Dr. Richard A. Flavell, Yale University School of Medicine
These CD11c-dnTGFβRII transgenic mice express a dominant negative form of the human transforming growth factor, beta receptor II gene under the control of a CD11c (Itgax) promoter. This form of the receptor blocks transforming growth factor, beta (Tgfb) signalling when its expression is sufficiently high to interfere with the assembly of a functional signaling complex consisting of transforming growth factor beta and type II and type I transforming growth factor beta receptors. Expression of the transgene is detected by RT-PCR in CD11c-expressing cells, including natural killer (NK) cell and lymphoid/myeloid dendritic cell (DC) subsets. Expression is not detected in natural killer T cells (NKT) cells, T cells or B cells isolated from transgenic mice. Transgenic mice show a selective dysregulation of NK cell homeostasis due to the blockage of transforming growth factor, beta (Tgfb) signalling. Large numbers of NK cells capable of producing considerable levels of interferon gamma (IFN-g) lead to downstream T helper type 1 (TH1) cell polarization. Mice bearing this transgene are viable and fertile and show no abnormalities in development.
A transgenic vector carrying a CD11c (Itgax) mouse promoter driving the human dnTGFBRIII (Tgfbr2 transforming growth factor, beta receptor II) gene inserted into exon 3 of the rabbit beta globin gene was injected into (C57BL/6 x C3H)F1 hybrid fertilized eggs. The donating investigator reports that this line has been backcrossed more than 10 times to C57BL/6Ncr (see SNP note below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, at least 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Expressed Gene||TGFBR2, transforming growth factor beta receptor 2, human|
|Site of Expression|
|Allele Name||transgene insertion 1, Richard A Flavell|
|Allele Type||Transgenic (Dominant negative, Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||CD11cdnR; Cd11cdnTGFBR2; CD11c-dnTGFBRII|
|Gene Symbol and Name||Tg(Itgax-TGFBR2)1Flv, transgene insertion 1, Richard A Flavell|
|Promoter||Itgax, integrin alpha X, mouse, laboratory|
|Expressed Gene||TGFBR2, transforming growth factor beta receptor 2, human|
|Strain of Origin||(C57BL/6 x C3H)F1|
|Molecular Note||The human TGFBRIII (Tgfbr2 transforming growth factor, beta receptor II) gene sequence between nucleotides -7 to +573 encoding the extracellular and transmembrane regions of TGFBR2 (dominant negative, dnTGFBR2) was inserted into exon 3 of the rabbit beta globin gene in the plasmid Itgax promoter vector pDOI-5. The construct was injected into (C57BL/6 x C3H)F1 hybrid fertilized eggs. RT-PCR confirmed expression of dnTGFBR2 in Itgax (CD11c)-expressing cells including subsets of natural killer cell (NK) and dendritic cell (DC) subsets. No expression is detected in NKT cells, T cells or B cells. Expression is sufficient to block TFG beta signaling through the functional receptor exclusively in DCs and NK cells.|
|Mutations Made By|| |
Dr. Richard Flavell, Yale University School of Medicine
When maintained as a live colony, hemizygotes may be bred with wildtype mice.
When using the B6.Cg-Tg(Itgax-TGFBR2)1Flv/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008378 in your Materials and Methods section.
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