B6(129S4)-Tg(tetO-Cxcl12,-tdTomato)#Forsb/Mmjax

Stock number: 035560
Product name: CXCL12 Tg , Tg-CXCL12(OE)
Research areas: Research Tools

Description

Tg-CXCL12(OE) transgenic mice may be bred to generate Tet-Off/Tet-On double mutant mice with conditional (inducible/reversible) spatial and temporal overexpression of the hematopoietic stem cell regulator Cxcl12 (C-X-C motif chemokine ligand 12) and a tdTomato reporter. This strain may be useful in studies of hematopoietic development, cancer and transplantation therapies.

Detailed description

Cxcl12 (C-X-C motif chemokine ligand 12) encodes a chemokine that functions as a major regulator of hematopoietic stem cell (HSC) trafficking, proliferation and survival. Tg-CXCL12(OE) mice express polyhistidine-tagged mouse Cxcl12 and a membrane bound tdTomato reporter under the control of a tetracycline-responsive promoter element (TRE; tetO). Mice hemizygous for the transgene are viable and fertile. The viability/fertility of homozygotes has not been determined.

When combined with a reverse tetracycline-controlled transactivator protein (rtTA) such as B6.Cg-Gt(ROSA)26Sor^{tm1(rtTA*M2)Jae}/J and induced with doxycycline, double mutant mice develop increased numbers of multipotent progenitors in the bone marrow and spleen, improved hematopoietic stem and progenitor cell mobilization into the blood as well as radioresistance of hematopoietic stem and progenitor cells.

Development

The transgenic construct contains a tetO (TRE) promoter directing expression of 6XHis tagged mouse Cxcl12 cDNA, a T2A cleavage site (mediates ribosomal skipping) and a tdTomato reporter. The linearized construct was microinjected into fertilized C57BL/6 oocytes. Founders were pooled and crossed to B6.Cg-Gt(ROSA)26Sor^{tm1(rtTA*M2)Jae}/J. Mice have been backcrossed to C57BL/6J for at least 5 generations by the donating laboratory (see SNP note below) and the rtTA transgene bred out. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

In 2021, 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 males sent to The Jackson Laboratory Repository. One of the 43 markers, on Chromosome 9, was segregating with 129. Also, one of the 5 markers that determine C57BL/6J from C57BL/6N was found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N;C57BL/6J genetic background.

Allele

Symbol: Tg(tetO-Cxcl12,-tdTomato)#Forsb
Name: transgene insertion, E Forsberg
MGI accession ID: MGI:6490253
Generation method: Transgenic
Attributes: Reporter; Inducible; Inserted expressed sequence; Epitope tag
Synonyms: TgCXCL12
Marker symbol: Tg(tetO-Cxcl12,-tdTomato)#Forsb
Marker name: transgene insertion, E Forsberg
Chromosome: UN
Strain of origin: C57BL/6
Site of expression: bone marrow and spleen

Molecular note: The transgenic construct contains a tetO (TRE) promoter directing expression of 6XHis tagged mouse Cxcl12 cDNA, a T2A cleavage site (mediates ribosomal skipping) and a tdTomato reporter. Founders were pooled.