B6.C-Cd79a^{tm3(cre/ERT2)Reth}/EhobJ

Stock number: 033026
Product name: mb1-CreER^T2
Research areas: Cancer Research, Research Tools

Description

mb1-CreER^T2 knock-in/Cd79a knock-out mice express a tamoxifen-inducible Cre recombinase from the endogenous promoter/enhancer elements of the Cd79a locus. When induced, Cre activity is observed in the B-cell lineage.

Detailed description

Cd79a (CD79A antigen (immunoglobulin-associated alpha)) encodes the immunoglobulin-alpha subunit of the B lymphocyte antigen receptor. Mutations in this gene have been associated with agammaglobulinemia-3.

In this mb1-CreER^T2 allele, expression of the targeted Cd79a gene is knocked out and tamoxifen-inducible CreER^T2 is expressed under the control of the Cd79a promoter/enhancer elements. Mice homozygous for this knock-in/knock-out allele are viable and fertile. When bred with mice containing a loxP-flanked sequence of interest, tamoxifen-induced, Cre recombinase-mediated excision of the floxed sequences occurs in the B-cell lineage.

For example, when bred with mice carrying a Syk floxed allele (Syk^tm1.2Tara, Stock No. 017309), resultant progeny induced with tamoxifen for 3 weeks are reported to demonstrate a loss of pre-B and immature B cells from bone marrow, and all transitional and marginal zone B cells and approximately 80% of follicular B cells are lost from the spleen.

Dr. Michael Reth and Dr. Elias Hobeika would appreciate acknowledgement in publications applying this research model.

The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be co-administered.

Development

CreER^T2, a fusion of Cre recombinase and an estrogen receptor ligand-binding domain modified to bind tamoxifen, was introduced to exon 2 of the mouse Cd79a gene via homologous recombination in BALB/c-derived embryonic stem (ES) cells. The start codon of Cd79a was also ablated, and a newly-generated start codon and an SV40 polyA signal were inserted immediately upstream of the CreER^T2 cDNA. The resulting mice were backcrossed to C57BL/6 for approximately 40 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. C57BL/6J (Stock No. 000664) is used to generate and maintain live animals.

Allele

Symbol: Cd79a^{tm3(cre/ERT2)Reth}
Name: targeted mutation 3, Michael Reth
MGI accession ID: MGI:5568505
Generation method: Targeted
Attributes: Recombinase-expressing; Inducible
Synonyms: mb1-CreER^T2; MCE
Marker symbol: Cd79a
Marker name: CD79A antigen (immunoglobulin-associated alpha)
Marker synonyms: Cd79al; Ig alpha; Iga; Igalpha; Ig-alpha; Ly54; Ly-54; MB1; mb-1
Chromosome: 7
Strain of origin: BALB/c
Molecular note: A cDNA encoding the tamoxifen-inducible cre recombinase (cre/ERT2) was knocked into exon 2.