STOCK Glp1r^{tm1.1(cre)Lbrl}/RcngJ

Stock number: 029283
Product name: Glp1r-ires-Cre
Research areas: Internal/Organ Research, Neurobiology Research, Research Tools

Description

Glp1r-ires-Cre knock-in mice express Cre recombinase under the direction of the Glp1r promoter in vagal sensory neurons in the gastrointestinal tract that respond to gastric and intestinal distension.

Detailed description

Glp1r-ires-Cre mice have an IRES-Cre fusion protein inserted 3 base pairs downstream of the stop codon of the glucagon-like peptide 1 receptor (Glp1r) gene. The presence of IRES-Cre cassette downstream of the stop codon allows for expression of GLP1R and cre. GLP1R encodes a receptor present on many cell types including pancreatic β cells, subsets of neurons in the central nervous system, as well as a subset of vagal sensory neurons that project to the gastrointestinal tract and act as mechanoreceptors, responsive to gastric and intestinal distension. Homozygous mice are viable and fertile. When these mice are bred with mice containing loxP-flanked sequence, Cre-mediated recombination will result in deletion of the floxed sequences in the Cre-expressing cells of the offspring.

When Glp1r-ires-Cre mice were bred to B6;129S-Gt(ROSA)26Sor^{tm32(CAG-COP4*H134R/EYFP)Hze}/J (Stock No. 012569) mice, which express a cre-inducible improved channelrhodopsin-2/EYFP fusion protein, optogenetic activation of GLP1R neurons results in increased gastric pressure, with a small change in breathing and heart rate.

 

Development

A targeting construct was designed by Stephen Liberles (Harvard Medical School) to insert an internal ribosomal entry site (IRES) fused to Cre Recombinase with a polyadenylation signal, followed by a frt-flanked neomycin resistance (neo) cassette, 3 base pairs downstream of the stop codon of the glucagon-like peptide 1 receptor (Glp1r) gene. This construct was electroporated into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric males were bred to B6;SJL-Tg(ACTFLPe)9205Dym/J mice (Stock No. 003800) to remove the neo cassette. Offspring were crossed to remove the flpe-expressing transgene, and resulting Glp1r-ires-Cre mice were bred to C57BL/6J mice for at least 1 generation. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Glp1r^{tm1.1(cre)Lbrl}
Name: targeted mutation 1.1, Stephen Liberles
MGI accession ID: MGI:5776617
Generation method: Targeted
Attributes: Recombinase-expressing
Marker symbol: Glp1r
Marker name: glucagon-like peptide 1 receptor
Chromosome: 17
Strain of origin: 129S6/SvEvTac
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Glp1r encodes a receptor present on many cell types including pancreatic Β cells, subsets of neurons in the central nervous system, as well as a subset of vagal sensory neurons that project to the gastrointestinal tract.
Molecular note: A cassette encoding IRES, Cre recombinase, and an FRT-flanked neomycin selection cassette is inserted into the mouse Glp1r locus 3 base pairs downstream of the coding sequence stop codon.