C57BL/6-Tg(Crhr1-icre,-tdTomato)3Njus/J

Stock number: 038650
Product name: Crfr1-cre
Research areas: Neurobiology Research, Research Tools

Description

Crfr1-cre transgenic mice express icre and tdTomato under the control of the mouse Crhr1 promoter in neurons in the hypothalamic paraventricular nucleus (PVN). They may be useful for visualizing and studying growth and differentiation of CRFR1+ cells and neurons and their role of this microcircuit in regulating hypothalamic-pituitary-adrenal axis activity during stress responses.

Detailed description

Crfr1-cre transgenic mice express a codon-optomized cre recombinase (icre) and tdTomato, separated by a P2A self-cleaving peptide, under the control of the mouse corticotropin releasing hormone receptor 1 (Crhr1) promoter. Crhr1, also known as corticotropin-releasing factor receptor (Crf1r), encodes a G-protein coupled receptor that is the primary receptor for the neuropeptide, corticotropin-releasing factor (CRF). CRF is expressed in the central nervous system, with high expression in the cortex, cerebellum, hippocampus and amygdala where it activates signal transduction pathways that regulate processes including stress, reproduction, immune response and obesity. When crossed with a strain containing loxP site-flanked sequences, icre-mediated recombination will result in deletion of the floxed sequences in the cre-expressing cells of the offspring.

In these mice, icre and tdTomato allow tracking of CRFR1-expressing cells both within the PVN and at distal targets. tdTomato is visible by direct fluorescence and by using immunohistochemistry. These mice are useful for studying growth and differentiation of CRFR1+ cells and neurons, and they help establish the role of this microcircuit in regulating hypothalamic-pituitary-adrenal axis activity.

Hemizygous and homozygous mice are viable and fertile.

Development

A bacterial artificial chromosome (BAC) library, RP23-239f10, was used to obtain mouse genomic DNA containing the entire mouse corticotropin releasing hormone receptor 1 (Crhr1) gene. This BAC was modified to insert a cassette containing (from 5' to 3') a codon-optomized cre recombinase sequence (icre), a P2A self-cleaving peptide, and a red fluorescent protein sequence (tdTomato) followed by a polyadenylation signal into the first exon at the ATG site of Crhr1. The linearized BAC was microinjected into fertilized C57BL/6 oocytes. Crfr1-cre founder mice were maintained by breeding transgenic mice with C57BL/6 mice for at least 10 generations by the donating laboratory. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(Crhr1-icre,-tdTomato)3Njus
Name: transgene insertion 3, Nicholas J Justice
MGI accession ID: MGI:7439324
Generation method: Transgenic
Attributes: Recombinase-expressing; Reporter
Synonyms: Crfr1-cre
Marker symbol: Tg(Crhr1-icre,-tdTomato)3Njus
Marker name: transgene insertion 3, Nicholas J Justice
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: A BAC (rp23-239f10) containing the entire genomic locus of mouse Crhr1 was modified using recombineering. A cassette encoding iCre-p2A-tdTomato-PA was inserted in the first exon at the site of the ATG start codon for the Crhr1 gene. Three independent transgenic lines were recovered. Line 3 was established and used for analyses.