B6;129-Tg(Cdh5-cre)1Spe/J

Stock number: 017968
Product name: VEC-Cre
Research areas: Cardiovascular Research, Developmental Biology Research, Research Tools

Description

These VEC-cre transgenic mice express Cre recombinase under the control of a Cdh5 promoter with greater efficiency than other similar lines. They may have applications related to the study of hematopoietic stem cell lineages derived from vascular endothelial cells.

Detailed description

These VEC-Cre mice express Cre recombinase under the control of the cadherin 5 (Cdh5) promoter. CDH5, also called vascular endothelial cadherin (VEC), is a calcium-dependent cell-cell glycoprotein expressed in the vasculature. VEC plays a role in endothelial cohesion and organization of the intercellular junctions. Since blood is derived from vasculature, VEC-Cre will mark both endothelial cells and blood cells in lineage tracing experiments using reporter lines such as B6.129X1-Gt(ROSA)26Sor^tm1(EYFP)Cos/J (Stock No. 006148). Hemizygotes are viable and fertile. When crossed with a strain containing a loxP site-flanked sequence, cre-mediated recombination results in deletion of the flanked sequence in the yolk sac and vasculature beginning at E9.5-E10.5, and in 85% of fetal liver cells beginning at E15.5. Also, 96% adult blood cells are derived from progenitors that have expressed cre. For example, when bred to B6;129-Runx1^tm3.1Spe/J mice (Stock No. 010673), 65% of the resulting mice die prior to birth with central nervous system hemorrhaging and fetal liver anemia, as compared to 100% of mice with germline deletion of Runx1.

Cre activity is seen in 85% of the fetal liver population and 96% of adult bone marrow. These mice exhibit more efficient cre-mediated recombination than B6.Cg-Tg(Cdh5-cre)7Mlia/J mice (Stock No. 006137), in which cre activity is seen in only 20%-40% of the fetal liver population and 52% of the adult bone marrow.

Development

A transgenic construct was designed to contain cre coding sequence under the control of the cadherin 5 (Cdh5) promoter, flanked by two genomic insulators derived from the chicken gamma-globulin gene. This transgene was introduced into (C57BL/6J x 129S1/SvImJ)F1 donor oocytes. The resulting VEC-Cre offspring were bred to (C57BL/6J x 129S1/SvImJ)F1 mice, and subsequently to B6.129X1-Gt(ROSA)26Sor^tm1(EYFP)Cos/J (Stock No. 006148) mice and B6;129-Runx1^tm3.1Spe/J (Stock No. 010673) mice. These triple mutant mice were then bred to (C57BL/6J x 129S1/SvImJ)F1 mice to separate the mutations. Mice carrying only the VEC-cre transgene were bred to (C57BL/6J x 129S1/SvImJ)F1 mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J mice (Stock No. 000664) to establish the colony.

Allele

Symbol: Tg(Cdh5-cre)1Spe
Name: transgene insertion 1, Nancy A Speck
MGI accession ID: MGI:3836418
Generation method: Transgenic
Attributes: Recombinase-expressing
Marker symbol: Tg(Cdh5-cre)1Spe
Marker name: transgene insertion 1, Nancy A Speck
Chromosome: UN
Strain of origin: (C57BL/6J x 129S1/SvImJ)F1
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: When crossed with cre-reporter strains, cre expression was detected in the yolk sac and vasculature of E9.5-E10.5 conceptus, and in the liver of E15.5 fetuses.
Molecular note: 2.5 Kb of the Cdh5 promoter was fused to a cre recombinase gene and placed between two genomic insulators derived from the chicken gamma-globulin gene. When crossed with cre-reporter strains, cre expression was detected in the yolk sac and vasculature of E9.5-E10.5 conceptus, and in the liver of E15.5 fetuses. Nearly all adult blood cells from mice carrying this transgene are derived from progentiors that have expressed cre.