C57BL/6-Tg(Nmur1-iCre,-eGFP)1Dart/J

Stock number: 038197
Product name: Nmur1^iCre-eGFP
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

Nmur1^iCre-eGFP mice express iCre and eGFP driven by the neuromedin U receptor 1 (Nmur1) promoter. When these mice are bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequences in Nmur1-expressing cells of the offspring (Tsou et al., Nature 2022). These mice also express eGFP in Nmur1-expressing cells. These Nmur1^iCre-eGFP mice may be useful for studying function and lineage mapping of Nmur1-positive cells.

Detailed description

Neuromedin U receptors (NMUR) are a group of G_q/11-protein-coupled receptors that include two subtypes, NMUR1 and NMUR2, each coded by a unique gene (Nmur1 and Nmur2, respectively). NMUR1 is expressed in peripheral tissues while NMUR2 is expressed primarily in the central nervous system (CNS). In mice, NMUR1 expression was shown in a subset of innate lymphoid cells (ILC2) in intestinal and lung tissue. The endogenous ligands for these receptors, neuromedin U and neuromedin S, are neuropeptides produced by cholinergic neurons. Stimulation of NMUR1 by its ligand is believed to regulate multiple physiological processes including type 2 inflammation and tissue repair, as well as insulin secretion.

Nmur1^iCre-eGFP transgenic mice express an improved Cre recombinase (iCre) and an enhanced GFP (eGFP) under the control of the neuromedin U receptor 1 (Nmur1) promoter/enhancer elements (Tsou et al., Nature 2022). When these transgenic mice are bred with mice containing loxP-flanked sequences, Cre-recombinase activity is detected in Nmur1-expressing cells of the offspring. The Nmur1^iCre-eGFP mice also express eGFP in Nmur1-expressing cells. Hemizygous Nmur1^iCre-eGFP mice are viable and fertile with no overt phenotype. The donating laboratory has not attempted to produce homozygous Nmur1^iCre-eGFP transgenic mice to date (April 2023).

The donating investigator has indicated that eGFP expression is detectable by flow cytometry. Flow cytometry analysis completed by the donating laboratory confirmed eGFP expression in intestinal ILC2s with minimal to no expression observed in other immune cell populations. It was also found that eGFP expression was exclusive to ILC2s in both non-lymphoid and lymphoid tissues. The donating laboratory has also verified Cre-recombinase activity by crossing Nmur1^iCre-eGFP to ROSA26iDTR mice (Stock No. 007900), which resulted in successful ablation of Nmur1-expressing ILC2s in the small intestine, colon, mesenteric lymph nodes (MLNs) and spleen after diphtheria toxin (DT) injection. These transgenic mice may be useful for studying the expression and function of Nmur1-expressing cells.

Note that copy number and insertion site is not known for this Nmur1^iCre-eGFP transgenic model to date (April 2023).

Development

The Nmur1^iCre-eGFP transgene was generated by replacing exons 2 and 3 of neuromedin U receptor 1 (Nmur1 gene), in the mouse BAC RP23-403I3, with a P2A-iCre-T2A-EGFP cassette followed by an FRT-flanked Kanamycin cassette. The FRT-flanked kanamycin cassette was removed by FLP-mediated recombination. The modified BAC construct was microinjected into the pronucleus of C57BL/6 zygotes and randomly integrated into the mouse genome. Founder line 1 was established and then subsequently maintained on a C57BL/6J background 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.

Allele

Symbol: Tg(Nmur1-icre,-EGFP)1Dart
Name: transgene insertion 1, David Artis
MGI accession ID: MGI:7464238
Generation method: Transgenic
Attributes: Recombinase-expressing; Reporter
Synonyms: Nmur1^iCre-eGFP; Tg(Nmur1-iCre,-eGFP)1Dart
Marker symbol: Tg(Nmur1-icre,-EGFP)1Dart
Marker name: transgene insertion 1, David Artis
Chromosome: UN
Strain of origin: C57BL/6
Molecular note: The transgene was generated by replacing exons 2 and 3 of neuromedin U receptor 1 (Nmur1 gene), in the mouse BAC RP23-403I3, with a P2A-iCre-T2A-EGFP cassette followed by an FRT-flanked Kanamycin cassette. The FRT flanked kanamycin cassette was removed by FLP-mediated recombination. The modified BAC construct was microinjected into the pronucleus of C57BL/6 zygotes and randomly integrated into the mouse genome. Founder line 1 was established and then subsequently maintained