C57BL/6-Tg(Tal1-cre/ERT)1Jrg/J

Stock number: 037467
Product name: endothelial-SCL-Cre-ER^T
Research areas: Hematological Research, Research Tools

Description

Endothelial-SCL-Cre-ER^T mice express Cre/ERT fusion protein driven by 5'-endothelial-SCL enhancer element. These mice may be useful for lineage mapping of endothelial cells.

Detailed description

Endothelial-SCL-Cre-ER^T transgenic mice express an inducible Cre recombinase (cre/ERT) under the control of the 5'-endothelial- stem cell enhancer (Scl) and promoter. The Scl, also known as T cell acute lymphocytic leukemia 1 (Tal1), encodes a transcription factor that regulates hematopoiesis and endothelial development in embryos and adults. There are multiple SCL stem-cell enhancers responsible for TAL1 expression, notably the 5'-endothelial-stem cell enhancer element drives expression in endothelial cells. Restricted to the cytoplasm, cre-ERT can only gain access to the nuclear compartment after exposure to tamoxifen. Hemizygous endothelial-SCL-Cre-ER^T mice are viable and fertile. When endothelial-SCL-Cre-ER^T mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Cre-expressing cells of the offspring. With this line (Line1), Cre recombination occurs specifically in almost all endothelial cells of the developing vasculature beginning at embryonic day 9.5 and in endothelial cells of the myocardium, lung, kidney, muscle, fat, intestine, liver portal tract, and brain after embryonic or adult tamoxifen administration respectively. Of note, the donating investigator indicated that recombination was observed in non-blood vessel area of the brain, specifically the granular layer of the cerebellum. It was also found that a third of endothelial-SCL-Cre-ER^T adult mice (N=6) had rare L-galactosidase (LacZ)-positive cells detected in lung tissue prior to tamoxifen exposure.

When bred with Rosa26 reporter strains (such as R26R (Stock No. 003474) and R26R-EYFP (Stock No. 006148)), Tal1-expressing cells can be permanently marked upon tamoxifen injection.

The donating investigator has made two inducible Tal1 transgenic lines available: HSC-SCL-CreER^T (Stock No. 037466), where Cre-mediated recombination occurs primarily in the hematopoietic stem cells and endothelial-SCL-Cre-ER^T (Stock No. 037467), where Cre-mediated recombination occurs primarily in most, but not all, endothelial cells.

Development

A transgenic construct containing the 6.1-kb murine SCL genomic fragment (from 7 to 0.9 kb relative to the transcriptional start in exon Ia) was cloned upstream of the SV40 minimal promoter (SV) and the Cre-ERT cassette including a rabbit -globin intron, was injected in to fertilized C57BL/6 oocytes (Ozgene). Endothelial-SCL-Cre-ER^T mice from founder line 1 were established and then subsequently maintained on C57BL/6 background (Harlan Laboratories, Inc./Envigo) for 15 generations by the donating laboratory. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J (Stock No. 000664) oocytes. Of note, the transgenic insertion site is unknown.

Allele

Symbol: Tg(Tal1-cre/ERT)1Jrg
Name: transgene insertion 1, Joachim R Gothert
MGI accession ID: MGI:3055721
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Marker symbol: Tg(Tal1-cre/ERT)1Jrg
Marker name: transgene insertion 1, Joachim R Gothert
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: The transgene is composed of the 5' Tal1 enhancer element (from -7 to -0.9 kb relative to the transcription start site in exon 1a), the SV40 minimal promoter, and the Cre-ER^T cassette, including a rabbit Beta-globin intron. The enhancer element drove the endothelial-specific expression of the transgene. Cre was active in the presence of tamoxifen.