The Npr3 gene encodes the natriuretic peptide receptor 3 (NPR3). Natriutetic peptides are small peptides which regulate blood volume and pressure, pulmonary hypertension, and cardiac function as well as some metabolic and growth processes. The Npr3-IRES2-CreERT2-neo knock-in mutation has an IRES2 sequence and a cre/ERT2 gene inserted immediately downstream of the Npr3 translational STOP codon - this is designed to have the endogenous promoter/enhancer elements direct cre/ERT2 expression to NPR3+ cells. When Npr3-IRES2-CreERT2-neo mice are bred with mice containing lox-flanked sequences, tamoxifen-inducible cre-mediated recombination will result in deletion of the floxed sequences in Npr3-expressing cells in the offspring after. The donating investigator reports Cre recombinase expression/activity largely recapitulates the endogenous Npr3 gene expression in the brain. Specifically, creERT2 expression is observed to be enriched in cortical layer 5 and in restricted cell populations within the hippocampal formation after tamoxifen induction. They did not examine cre/ERT2 expression in tissues other than brain. This knock-in allele is designed to avoid disrupting expression of the endogenous protein; although Npr3 expression from the Npr3-IRES2-CreERT2-neo allele has not been evaluated to date. Heterozygous mice are viable and fertile with no reported gross physical or behavioral abnormalities. To date (January 2024), it has not been attempted to make this strain homozygous. This line, Stock No. 038956, is similar to Npr3-IRES2-Cre-neo mice (Stock No. <a href="https://www.jax.org/strain/038955">038955</a>), yet Stock No. 038956 contains a cre/ERT2 gene instead of the cre gene found in Npr3-IRES2-Cre-neo mice. Npr3-IRES2-CreERT2-neo mice exhibit a more restricted expression pattern when compared to Npr3-IRES2-Cre-neo mice as very few cells are labelled in the cortex.

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Npr3-IRES2-CreERT2-neo knock-in mice are designed to have cre/ERT2 expression/activity directed by the endogenous natriuretic peptide receptor 3 promoter/enhancer sequences. In the brain, cre/ERT2 expression is observed to be enriched in cortical layer 5 and in restricted cell populations within the hippocampal formation. These mice may be used to generate conditional mutations for studying gain-or-loss of function and/or fate mapping in NPR3-expressing cells.

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