B6N.Cg-Tg(Cxcl12-icre/ERT2)L289Nono/J

Stock number: 036235
Product name: Cxcl12-iCreER
Research areas: Internal/Organ Research, Research Tools

Description

Cxcl12-creER transgenic mice express a tamoxifen-inducible (ERT2) codon-improved iCre recombinase directed by mouse Cxcl12 (chemokine (C-X-C motif) ligand 12) promoter elements. When induced, iCre recombinase activity is observed in a subset of bone marrow stromal cells. This strain may be useful for in vivo lineage tracing and functional analysis of skeletal regeneration.

Detailed description

These Cxcl12-creER transgenic mice express a tamoxifen inducible (ERT2) codon-improved iCre recombinase driven by the mouse Cxcl12 (chemokine (C-X-C motif) ligand 12) promoter.  Cxcl12 encodes a chemokine expressed by a subset of bone marrow stromal cells (BMSCs) and is involved in support of hematopoiesis and osteogenesis. The transgene insert contains a fusion product involving iCre recombinase and a mutant form of the mouse estrogen receptor ligand binding domain. The mutant estrogen receptor does not bind with natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen (4-OHT). Restricted to the cytoplasm, the iCre/ERT2 protein can only gain access to the nuclear compartment after exposure to 4-OHT, a metabolite of tamoxifen. When crossed with a strain containing loxP sites flanking the sequence of interest, the offspring are useful for generating tamoxifen-induced, iCre-mediated targeted gene deletions in Cxcl12-expressing cells. After tamoxifen induction, Cre recombinase activity is restricted to a subset of Cxcl12-expressing bone marrow stromal cells. The Donating Investigator reports that homozygous mutant mice are viable (fertility has not been assessed).

When combined with a reporter such as B6.Cg-Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/J (Stock No. 007914), this strain may be useful for in vivo lineage tracing.

Development

The bacterial artificial chromosome, RP23-22F6, containing 74 kb upstream and 121 kb downstream genomic sequences of the Cxcl12 gene was modified to insert a cDNA encoding (codon improved) iCre/ERT2 fusion protein followed by a bovine growth hormone and polyA sequence into the first exon of Cxcl12 to replace the start codon. The donating investigator has confirmed that the BAC includes two pseudogenes - LOC102631679 and Rpl28-ps4. This BAC was microinjected into the pronuclei of fertilized B6SJLF1 oocytes. Founder line L289 was bred to C57BL/6NCrl mice. Mice were backcrossed to C57BL/6NCrl for 12 generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6NJ oocytes (Stock No. 005304).

Allele

Symbol: Tg(Cxcl12-icre/ERT2)L289Nono
Name: transgene insertion L289, Noriaki Ono
MGI accession ID: MGI:6508084
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: Cxcl12-creER
Marker symbol: Tg(Cxcl12-icre/ERT2)L289Nono
Marker name: transgene insertion L289, Noriaki Ono
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F1
Molecular note: The bacterial artificial chromosome, RP23-22F6, containing 74 kb upstream and 121 kb downstream genomic sequences of the Cxcl12 gene was modified to insert (codon improved) icre/ERT2 fusion followed by bovine growth hormone and polyA cDNA into the first exon.