Cre-mediated excision of a floxed Stop cassette in these zDC-loxStoplox-DTR mice enables expression of the human diptheria toxin receptor (DTR) from the mouse Zbtb46 promoter. Classical dendritic cells (cDCs) can be specifically depleted from non-bone marrow chimeras through diptheria toxin (DT) treatment.
Michel C Nussenzweig, The Rockefeller University
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Spontaneous (Null/Knockout) | Tyr | tyrosinase |
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence) | Zbtb46 | zinc finger and BTB domain containing 46 |
Zbtb46 (zinc finger and BTB domain containing 46; also known as zDC or Btbd4) is a classical dendritic cell (cDC)-restricted zinc finger transcription factor that is not expressed by other immune cell populations, including plasmacytoid dendritic cells, monocytes, or macrophages. It acts primarily as a negative regulator of cDC gene expression.
In this targeted mutant strain, a loxP-Stop-loxP-IRES-DTR (human diptheria toxin receptor)-mCherry cassette was inserted into the 3' UTR of the Zbtb46 locus. Crossing these animals with Cre-expressing mice results in the excision of the transcriptional stop element and in DTR expression in Zbtb46-expressing cells. This mouse strain is useful to deplete cDCs in non-bone marrow chimeras. It has been demonstrated that progeny of animals crossed with Csf1r-Cre mice can be injected with diptheria toxin (DT) to deplete classical dendritic cells. The mCherry is not expressed effectively after excision of the excision of the Stop element and these mice should not be used as reporter animals.
An FRT-flanked neomycin resistance cassette and a loxP-Stop-loxP-IRES-DTR (human diptheria toxin receptor)-mCherry element were introduced to exon 5, immediately after the stop codon. The mutation was created via homologous recombination in B6(Cg)-Tyrc-2J-derived CY2.4 ES cells. Resulting male chimeric mice were crossed to Flp-expressing mice on an albino C57BL/6 background to excise the neomycin cassette. This strain was maintained on an albino C57BL/6 genetic background by the donating laboratory.
Expressed Gene | RFP, Red Fluorescent Protein, coral |
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Site of Expression | Crossing these animals with Cre-expressing mice results in the excision of the transcriptional Stop element, however mCherry is not expressed effectively after excision of the Stop element |
Allele Name | albino 2 Jackson |
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Allele Type | Spontaneous (Null/Knockout) |
Allele Synonym(s) | |
Gene Symbol and Name | Tyr, tyrosinase |
Gene Synonym(s) | |
Site of Expression | Expressed in melanosomes |
Strain of Origin | B6.Cg-Tyrp1b Hps1ep |
Chromosome | 7 |
Molecular Note | This mutation has a G-to-T base change at coding nucleotide 230 resulting in an amino acid change from arginine to leucine at residue 77 (p.R77L) which lies in the highly conserved DDRE sequence. Nucleotide 230 is at the alternative 5' splice donor site for exon 1 and this allele does not produce the 1a or 1b subset of tyrosinase transcripts but does produce a significant increase in 1c and 1d transcripts. Western blots of homozygous mutant skin extracts demostrate the nearly complete absence of the broad 76-84 kDa band of glycosylated wild-type tyrosinase. No tyrosinase activity was found in hairbulb extracts from homozygous mice. |
Allele Name | targeted mutation 4, Michel C Nussenzweig |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence) |
Allele Synonym(s) | zDCLSLDTR |
Gene Symbol and Name | Zbtb46, zinc finger and BTB domain containing 46 |
Gene Synonym(s) | |
Expressed Gene | RFP, Red Fluorescent Protein, coral |
Site of Expression | Crossing these animals with Cre-expressing mice results in the excision of the transcriptional Stop element, however mCherry is not expressed effectively after excision of the Stop element |
Strain of Origin | B6(Cg)-Tyrc-2J |
Chromosome | 2 |
Molecular Note | An FRT-flanked neomycin resistance cassette and a loxP-Stop-loxP-IRES-DTR (human diptheria toxin receptor)-mCherry element were introduced to exon 5, immediately after the stop codon. The mCherry is not expressed effectively after excision of the excision of the Stop element and mice should not be used as reporter animals. Flp-mediated recombination removed the FRT-flanked neo cassette. |
Heterozygotes and homozygotes are viable and fertile.
When using the zDC-loxStoplox-DTR mouse strain in a publication, please cite the originating article(s) and include JAX stock #028539 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Zbtb46<tm4.1(HBEGF)Mnz> |
Frozen Mouse Embryo | B6.Cg-Zbtb46<tm4.1(HBEGF)Mnz> Tyr<c-2J>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Zbtb46<tm4.1(HBEGF)Mnz> Tyr<c-2J>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Zbtb46<tm4.1(HBEGF)Mnz> Tyr<c-2J>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.Cg-Zbtb46<tm4.1(HBEGF)Mnz> Tyr<c-2J>/J Frozen Embryo | $3373.50 |
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