AgRP-IRES-Cre knock-in mice have IRES-Cre inserted downstream of the stop codon of the agouti related neuropeptide locus. Cre recombinase expression is observed in agouti-related protein secreting neurons. These mice may be useful for studying the physiological functions of GABA neurotransmission in agouti-related protein neurons in the hypothalamus.
Bradford B. Lowell, Beth Israel Deaconess Med Cntr (Harvard)
Genetic Background | Generation |
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F?+F21
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Recombinase-expressing) | Agrp | agouti related neuropeptide |
Mice homozygous for the AgRP-IRES-Cre knock-in allele are viable and fertile, with IRES-Cre inserted downstream of the Agrp stop codon. As such, cre expression is directed by the endogenous promoter/enhancer regions. Specifically, Cre recombinase expression is observed in agouti-related protein (AgRP) secreting neurons. When bred with mice containing a loxP-flanked sequence of interest, Cre-mediated recombination will result in deletion of the floxed sequence(s) in the offspring. These mice may be useful for studying the physiological functions of GABA neurotransmission in ArGP neurons in the hypothalamus.
When AgRP-IRES-Cre mice are bred to have Cre-inducible channelrhodopsin/EYFP expression (e.g., Ai32 [Stock Nos. 012569/024109]), the resulting double mutant animals allow manipulation of AgRP-expressing neuron dynamics (sensory and post-ingestive signals) in response to caloric food and/or experimental compound consumption [Su, Alhadeff and Betley 2017 Cell Rep. 21:2724].
The AgRP-IRES-Cre knock-in allele was created to have an IRES-Cre inserted after the stop codon of the agouti related neuropeptide locus (Agrp) on chromosome 8. The specific details are below.
The targeting vector contained an internal ribosome entry site (IRES) fused to a Cre recombinase gene, followed by a frt-flanked kanamycin/neomycin (kan/neo) resistance cassette. This was targeted downstream of the Agrp stop codon (originally identified as being in exon 3, but more recent exon numbering refers to this same exon as exon 5). The construct was electroporated into W4-derived 129S6/SvEvTac embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and resulting chimeric males were bred to C57BL/6 x 129 or FVB females. Offspring were bred with Flp-expressing mice (129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J [Stock No. 003946]) for germline deletion of the kan/neo cassette. Progeny were crossed to remove the Flp-expressing allele. Mice from the resulting AgRP-IRES-Cre colony were sent to The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish our live colony.
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
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Site of Expression | agouti-related protein (AgRP) neurons of the brain |
Allele Name | targeted mutation 1, Bradford B Lowell |
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Allele Type | Targeted (Recombinase-expressing) |
Allele Synonym(s) | Agrp-Cre; Agrp-Ires-cre |
Gene Symbol and Name | Agrp, agouti related neuropeptide |
Gene Synonym(s) | |
Expressed Gene | cre, cre recombinase, bacteriophage P1 |
Site of Expression | agouti-related protein (AgRP) neurons of the brain |
Strain of Origin | 129S6/SvEvTac |
Chromosome | 8 |
Molecular Note | An IRES-cre-frt-kan/neo-frt cassette was inserted in frame in exon 5 after the stop codon via homologous recombination. The kan/neo cassette was subsequently removed via in vivo Flp mediated recombination. Crosses to reporter mice detected Cre activity in AGRP+ neurons. |
Mutations Made By | Bradford Lowell, Beth Israel Deaconess Med Cntr (Harvard) |
When maintaining a live colony, homozygous mice may be bred together.
When using the Agrp-Ires-cre mouse strain in a publication, please cite the originating article(s) and include JAX stock #012899 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Agrp<tm1(cre)Lowl> |
Frozen Mouse Embryo | STOCK Agrp<tm1(cre)Lowl>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Agrp<tm1(cre)Lowl>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | STOCK Agrp<tm1(cre)Lowl>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | STOCK Agrp<tm1(cre)Lowl>/J Frozen Embryo | $3373.50 |
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