STOCK Cyp19a1^tm1.1Vdlm/DbrnJ

Stock number: 039883
Product name: Cyp19a1 loxP
Research areas: Developmental Biology Research, Neurobiology Research, Research Tools

Description

CYP19a1 loxP mice have loxP sites flanking exons 10-11 of the Cyp19a1 gene. These mice may be useful when studying the role of neuron-derived 17Β-estradiol (E2) in regulating synaptic plasticity and cognitive function in the male and female brain.

Detailed description

CYP19a1 loxP mice have loxP sites flanking exons 10-11 of the cytochrome P450, family 19, subfamily a, polypeptide 1 (Cyp19a1) gene. Cyp19a1, also called aromatase, encodes an enzyme localized to the endoplasmic reticulum which catalyzes the last steps of the conversion of testosterone to 17Β-estradiol (E2). E2 is produced in the ovary and is also produced in the male and female brain, with high concentrations produced in the hypothalamus, amygdala, hippocampus, and cerebral cortex due to expression of aromatase. E2 has been implicated in both neurotrophic and neuroprotective actions in the brain, including modulation of reproductive behavior, synaptic plasticity, neuroprotection, and cognition.

Homozygous CYP19a1 loxP mice are viable and fertile. The floxed region includes 3318 bp of the coding sequence including the second substrate-binding site, the iron-binding site, and part of the p450 domain and the poly A signal.

Development

CYP19a1 loxP mice were created in collaboration between Dr. Ratna Vadlamudi (University of Texas Health) and Dr. Darrell Brann (Augusta University). The CYP19a1 loxP targeting vector was designed to insert a loxP site followed by an FRT-flanked neomycin resistance (neo) cassette upstream of exon 10 of the cytochrome P450, family 19, subfamily a, polypeptide 1 (Cyp19a1) gene. A second loxP site was inserted downstream of exon 11. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the chimeric mice were bred to C57BL/6 Flp deleter mice to remove the neo cassette. Resulting CYP19a1 loxP offspring were bred to C57BL/6J mice for at least 7 generations by the donating laboratory (see SNP note below). Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

In 2024, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the males sent to The Jackson Laboratory Repository. Six of the 43 markers throughout the genome were segregating with 129. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Cyp19a1^tm1.1Vdlm
Name: targeted mutation 1.1, Ratna K Vadlamudi
MGI accession ID: MGI:7486738
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Aro Flox; CYP19a1 loxP; Cyp19a1^tm1.1Geno
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: 129
Molecular note: Exons 10 and 11 were flanked by loxP sites. An FRT-flanked neomycin selection cassette was inserted after the first loxP site, upstream of exon 10, and was removed via flp-mediated recombination. Exons 10-11 encode for the second substrate-binding site, the iron-binding site, part of the p450 domain, and the polyA signal.