B6.Cg-Zbtb46^{tm4.1(HBEGF)Mnz} Tyr^c-2J/J

Stock number: 028539
Product name: zDC-loxStoplox-DTR
Research areas: Dermatology Research, Mouse/Human Gene Homologs, Research Tools, Sensorineural Research

Description

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.

Detailed description

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.

Development

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)-Tyr^c-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.

Allele

Symbol: Tyr^c-2J
Name: albino 2 Jackson
MGI accession ID: MGI:1855985
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Tyr
Marker name: tyrosinase
Chromosome: 7
Strain of origin: B6.Cg-Tyrp1^b Hps1^ep
Site of expression: Expressed in melanosomes
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

Symbol: Zbtb46^{tm4.1(HBEGF)Mnz}
Name: targeted mutation 4, Michel C Nussenzweig
MGI accession ID: MGI:5749237
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Inserted expressed sequence
Marker symbol: Zbtb46
Marker name: zinc finger and BTB domain containing 46
Chromosome: 2
Strain of origin: B6(Cg)-Tyr^c-2J
Expressed genes: 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
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.