Epitope-tagged and phosphomimetic mouse models for investigating natriuretic peptide-stimulated receptor guanylyl cyclases

Jeremy R. Egbert, Tracy F. Uliasz, Katie M. Lowther, Deborah Kaback, Brandon M Wagner, Chastity L Healy, Timothy D. O’Connell, Lincoln R. Potter, Laurinda A. Jaffe, Siu Pok Yee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The natriuretic peptide receptors NPR1 and NPR2, also known as guanylyl cyclase A and guanylyl cyclase B, have critical functions in many signaling pathways, but much remains unknown about their localization and function in vivo. To facilitate studies of these proteins, we developed genetically modified mouse lines in which endogenous NPR1 and NPR2 were tagged with the HA epitope. To investigate the role of phosphorylation in regulating NPR1 and NPR2 guanylyl cyclase activity, we developed mouse lines in which regulatory serines and threonines were substituted with glutamates, to mimic the negative charge of the phosphorylated forms (NPR1-8E and NPR2-7E). Here we describe the generation and applications of these mice. We show that the HA-NPR1 and HA-NPR2 mice can be used to characterize the relative expression levels of these proteins in different tissues. We describe studies using the NPR2-7E mice that indicate that dephosphorylation of NPR2 transduces signaling pathways in ovary and bone, and studies using the NPR1-8E mice that indicate that the phosphorylation state of NPR1 is a regulator of heart, testis, and adrenal function.

Original languageEnglish (US)
Article number1007026
JournalFrontiers in Molecular Neuroscience
Volume15
DOIs
StatePublished - Oct 19 2022

Bibliographical note

Funding Information:
This study was supported by grants from the National Institutes of Health: R37 HD014939 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (LJ) and R01 HL130099 and R01 HL152215 from the National Heart, Lung, and Blood Institute (LP and TO’C). Additional funding was provided by grants from the Health Center Research Advisory Council (S-PY), the Fund for Science (LJ and LP), the Hormone Research Fund (LP), and by a University of Minnesota-Mayo Clinic Partnership Grant and a University of Minnesota Academic Health Center Faculty Research and Development Grant (LP).

Publisher Copyright:
Copyright © 2022 Egbert, Uliasz, Lowther, Kaback, Wagner, Healy, O’Connell, Potter, Jaffe and Yee.

Keywords

  • cyclic GMP
  • genetically modified mice
  • guanylyl cyclase
  • natriuretic peptide receptor
  • phosphorylation

PubMed: MeSH publication types

  • Journal Article

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