B6(FVB)-Cxcl12^tm1.1Link/J

Stock number: 021773
Research areas: Hematological Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Exon 2 of the mouse Cxcl12 (chemokine (C-X-C motif) ligand 12) gene is flanked by loxP sites in this conditional targeted mutation strain. Cre recombinase-mediated excision of the floxed region enables tissue/cell-specific knockouts of the gene, useful in studies of hematopoietic stem cell maintenance or other CXCL12-dependent processes.

Detailed description

Cxcl12 (chemokine (C-X-C motif) ligand 12) regulates many hematopoietic and non-hematopoietic cell types. CXCL12 is constitutively expressed at high levels in many bone marrow stromal cell types, where it contributes to both hematopoietic stem cell (HSC) and lymphoid progenitor maintenance. Exon 2 of the mouse gene is flanked by loxP sites in this conditional targeted mutation. Cre recombinase-mediated excision of the floxed region enables tissue/cell-specific knockouts of the gene, useful in studies of hematopoietic stem cell maintenance or other CXCL12-dependent processes.

Osx-Cre (Sp7-Cre, see Stock No. 006361)-mediated deletion of Cxcl12 from Sp7 transcription factor 7 (osterix)-expressing stromal cells, which include CXCL12-abundant reticular cells and osteoblasts, results in constitutive hematopoietic progenitor cell (HPC) mobilization and a loss of B-lymphoid progenitors, but HSC function is normal.

Tie2-Cre (Tek-Cre, see Stock No. 008863)- mediated deletion of Cxcl12 from endothelial cells results in a modest loss of long term repopulating activity.

Strikingly, deletion of Cxcl12 from mesenchymal progenitors using Prx1-Cre (Prrx1-Cre, see Stock No. 005584) is associated with a marked loss of HSCs, long term repopulating activity, HSC quiescence and common lymphoid progenitors.

Deletion of Cxcl12 from mineralizing osteoblasts via osteocalcin-Cre (BGLAP-Cre, see Stock No. 019509) crosses has no effect on HSCs or lymphoid progenitors.

Development

A targeting vector incorporating loxP-exon 2-loxP-PGK-neomycin-loxP sequences was introduced to C57BL/6NTac-derived B6/BLU (lacZ reporter) embryonic stem (ES) cells. Mice carrying this targeted allele were crossed with B6.FVB congenic EIIa-Cre mice (see Stock No. 003724), and offspring carrying the Neo-excised allele were identified. This strain was backcrossed to C57BL/6 for 10 or more generations by the donating lab.

A 48 SNP (single nucleotide polymorphism) panel analysis, with 43 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. One of the 5 markers that determine C57BL/6J from C57BL/6N was found to be segregating, on Chromosome 6. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Cxcl12^tm1.1Link
Name: targeted mutation 1.1, Daniel C Link
MGI accession ID: MGI:5468835
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Cxcl12
Marker name: chemokine (C-X-C motif) ligand 12
Chromosome: 6
Strain of origin: C57BL/6NTac-Tg(HBB-lacZ)ALey/Ley
Molecular note: A loxP site was inserted upstream of exon 2. A floxed neo cassette was inserted downstream of exon 2. Cre-mediated recombination removed the neo cassette and left exon 2 floxed.