C57BL/6-Tg(Esm1-icre/ERT2)27Rha/J

Stock number: 042005
Product name: Esm1(BAC)^iCreERT2
Research areas: Cardiovascular Research, Research Tools

Description

Esm1(BAC)^iCreERT2 mice express a codon-improved tamoxifen-inducible icre/ERT2 fusion gene under the control of the Esm1 promoter. This strain allows temporally controlled deletion of floxed genes in all tissues expressing Esm1. These mice are useful when studying formation of intestinal and mesenteric arteries during development and the role of endothelial cells in angiogenesis, inflammation, and vascular permeability.

Detailed description

Esm1(BAC)^iCreERT2 mice express a codon-improved tamoxifen-inducible icre/ERT2 fusion gene under the control of the endothelial cell-specific molecule 1 (Esm1) gene promoter and enhancer elements. ESM1 is a secreted glycoprotein which is mainly expressed and secreted by endothelial cells (ECs) in human lung and kidney tissues and renal epithelia. It is involved in angiogenesis and functions in inflammation and developing vasculature. It may have potent implications in lung endothelial cell-leukocyte interactions and may play a role in the onset of diabetic kidney disease (DKD), sepsis, and several cancer types.

Hemizygous mice are viable and fertile, the donating investigator did not produce a homozygous colony. When transgenic mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of loxP-flanked sequences in Esm1-expressing cells.

Esm1(BAC)^iCreERT2 transgenic mice were further bred to mTmG mice (Stock No. 007676), which express tdTomato prior to Cre-mediated deletion of a STOP cassette and express EGFP after Cre-mediated deletion of a STOP cassette. Following tamoxifen administration, EGFP-expressing ECs are abundant in large mesenteric arteries and smaller arterial branches near the intestinal wall. Also, retinas of these animals express EGFP in sprouting ECs and renal epithelia similar to the distribution of endogenous ESM1 protein.

Development

The Esm1(BAC)^iCreERT2 transgene was designed with the endothelial cell-specific molecule 1 (Esm1) gene promoter and enhancer elements from a BAC transgene driving expression of a icre/ERT2 fusion gene (codon-improved Cre recombinase fused to a human estrogen receptor ligand binding domain) followed by an SV40 polyadenylation signal. The transgene was microinjected into fertilized eggs from mice on a C57BL/6 genetic background and mice from founder line 27 were maintained by breeding mice to C57BL/6J mice (Stock No. 000664) for at least 20 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Tg(Esm1-icre/ERT2)27Rha
Name: transgene insertion 27, Ralf H Adams
MGI accession ID: MGI:7490347
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: Esm1(BAC)^iCreERT2; Esm1(PAC)CreERT2; Esm1^iCreERT2; Esm1-iCreERT2
Marker symbol: Tg(Esm1-icre/ERT2)27Rha
Marker name: transgene insertion 27, Ralf H Adams
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: The tamoxifen-inducible iCreERT2 was inserted into a start codon of the Esm1 gene in BAC clone RP24-560I14. Two founders were obtained of which only one (founder #27) presented transmission of the transgene to offspring.