B6.129S(SJL)-Cyp19a1^{tm2.1(cre)Shah}/J

Stock number: 027038
Product name: aro^Cre
Research areas: Neurobiology Research

Description

aro^Cre mice express Cre recombinase in portions of the amygdala. They may be useful in applications examining sexually dimorphic social behaviors.

Detailed description

aro^Cre mice express Cre recombinase under the direction of the Cyp19a1 (cytochrome P450, family 19, subfamily a, polypeptide 1) gene. The presence of cre does not affect the expression of Cyp19a1. CYP19A1 encodes aromatase, an enzyme responsible for the aromatization of androgens into estrogens in the brain. Aromatase is expressed in the posterodorsal medial amygdala of the male brain where it controls neural circuits underlying courtship vocalization, mating, aggression, and territory marking in male mice. Brains of female mice contain lower levels of aromatase. 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.

Injection of an adeno-associated virus (AAV) encoding Cre-dependent caspase-3 into mice carrying this aro^Cre and one copy of a aro^- allele triggers apoptosis exclusively in aromatase+ cells. Males show no changes in courtship or mating habits, but do show increased aggression towards other males. Females display increased maternal aggression towards intruders.

When injected with cre-dependent DREADD-Gi:mCherry, which inhibits GABAergic neurons, mice show increased latency of attack on other males.

Development

A targeting construct was designed to insert an internal ribosomal entry site (IRES) and a Cre Recombinase gene, followed by a frt-flanked neomycin resistance (neo) cassette into the 3’ UTR of the Cyp19a1 (cytochrome P450, family 19, subfamily a, polypeptide 1) gene. This construct was electroporated into 129/SvEv-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric males were bred to C57BL/6J females. Offspring were bred to B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice Stock No. 005703) and resulting progeny were crossed to remove the flp-expressing transgene. aro^Cre mice were backcrossed for at least 5 generations to C57BL/6J mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Cyp19a1^{tm2.1(cre)Shah}
Name: targeted mutation 2.1, Nirao Shah
MGI accession ID: MGI:5632151
Generation method: Targeted
Attributes: Recombinase-expressing
Synonyms: aro^Cre; aromatase^Cre
Marker symbol: Cyp19a1
Marker name: cytochrome P450, family 19, subfamily a, polypeptide 1
Marker synonyms: Ar; ArKO; ARO; ARO1; aromatase; CPV1; CYAR; CYP19; Cyp19a; CYPXIX; Int5; Int-5; p450arom; P-450AROM
Chromosome: 9
Strain of origin: 129S/SvEv
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: Cre recombinase is expressed in portions of the amygdala.
Molecular note: A targeting construct was designed to insert an internal ribosomal entry site (IRES) and a Cre recombinase gene, followed by a FRT-flanked neomycin resistance (neo) cassette downstream of the 3' UTR. Flp-mediated recombination removed the FRT-flanked neo cassette.