Register New MMRRC Account
Reset Password
Register for New Mouse Models
Click Here for Additional Contact Information
Availability & Fees Order this Strain
NPR2 (natriuretic peptide receptor 2) is the primary receptor for C-type natriuretic peptide (CNP), which, when bound to ligand increases guanylyl cyclase activity. NPR2 is involved in the regulation of bone growth and meiosis in oocytes; it is expressed in ovarian follicles, chondrocytes, adrenal, kidneys, lungs, hearts, testis, and epididymis tissues. Activation of NPR2 is CNP-dependent, inactivation requires dephosphorylation, which results in a decrease in cyclic GMP.
Npr2-7E mice have 7 glutamate substitutions in exons 8 and 9 of the Npr2 gene. The 7E point mutations are located in the juxta membrane domain and the beginning of the kinase homology domain and consist of 7 regulatory serines and threonines converted to glutamates: S489E, S513E, T516E, S518E, S523E, S526E, T529E. The mutations prevent NPR2 dephosphorylation and inactivation. Mice that are homozygous for this allele are viable and fertile. Female progeny have a delayed resumption of meiosis in response to luteinizing hormone, however, fertility is not affected. In addition, homozygous Npr2-7E mice have bones (tail, femur, tibia and body) that are 8-14% longer than controls. Increased limb and body length is visible as early as 4 weeks. By 18 weeks of age the fifth caudal vertebra is 18% larger than controls.
The Npr2-7E targeting vector was designed to insert a loxP site, a wild-type Npr2 mini gene with 200 bp of intron 8 and cDNA from exons 8-22 (from BAC vector, RP24-306K11 and full-length Npr2 cDNA), an IRES/EGFP reporter, an FRT-flanked PGK neomycin cassette and a loxP site into intron 7 and the insertion of the 7E point mutations into exons 8 and 9 of the natriuretic peptide receptor 2 (Npr2) locus on chromosome 4. The 7E point mutations consist of 7 glutamate substitutions: S489E, S513E, T516E, S518E, S523E, S526E, T529E. The construct was electroporated into (129Sv x C57BL/6J)F1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Chimeric males were crossed to B6.129S1-Hprttm1(CAG-cre)Mnn females to remove the Npr2 cDNA-EGFP-neo construct. The cre allele was later bred out of the strain. This strain is maintained on a B6 and 129 mixed background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.
Shuhaibar LC, Egbert JR, Edmund AB, Uliasz TF, Dickey DM, Yee SP, Potter LR, Jaffe LA. Dephosphorylation of juxtamembrane serines and threonines of the NPR2 guanylyl cyclase is required for rapid resumption of oocyte meiosis in response to luteinizing hormone. Dev Biol. 2016 Jan 1;409(1):194-201. doi: 10.1016/j.ydbio.2015.10.025. Epub 2015 Oct 30. (Medline PMID: 26522847)
Shuhaibar LC, Robinson JW, Vigone G, Shuhaibar NP, Egbert JR, Baena V, Uliasz TF, Kaback D, Yee SP, Feil R, Fisher MC, Dealy CN, Potter LR, Jaffe LA. Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor. Elife. 2017 Dec 4;6:e31343. doi: 10.7554/eLife.31343. (Medline PMID: 29199951)
Schmidt H, Dickey DM, Dumoulin A, Octave M, Robinson JW, Kühn R, Feil R, Potter LR, Rathjen FG. Regulation of the Natriuretic Peptide Receptor 2 (Npr2) by Phosphorylation of Juxtamembrane Serine and Threonine Residues Is Essential for Bifurcation of Sensory Axons. J Neurosci. 2018 Nov 7;38(45):9768-9780. doi: 10.1523/JNEUROSCI.0495-18.2018. Epub 2018 Sep 24. (Medline PMID: 30249793)
Robinson JW, Blixt NC, Norton A, Mansky KC, Ye Z, Aparicio C, Wagner BM, Benton AM, Warren GL, Khosla S, Gaddy D, Suva LJ, Potter LR. Male mice with elevated C-type natriuretic peptide-dependent guanylyl cyclase-B activity have increased osteoblasts, bone mass and bone strength. Bone. 2020 Jun;135:115320. doi: 10.1016/j.bone.2020.115320. Epub 2020 Mar 13. (Medline PMID: 32179168)
Wagner BM, Robinson JW, Lin YW, Lee YC, Kaci N, Legeai-Mallet L, Potter LR. Prevention of guanylyl cyclase-B dephosphorylation rescues achondroplastic dwarfism. JCI Insight. 2021 May 10;6(9):e147832. doi: 10.1172/jci.insight.147832. (Medline PMID: 33784257)
Wagner BM, Robinson JW, Prickett TCR, Espiner EA, Khosla S, Gaddy D, Suva LJ, Potter LR. Guanylyl Cyclase-B Dependent Bone Formation in Mice is Associated with Youth, Increased Osteoblasts, and Decreased Osteoclasts. Calcif Tissue Int. 2022 Nov;111(5):506-518. doi: 10.1007/s00223-022-01014-7. Epub 2022 Aug 10. (Medline PMID: 35947145)
Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Technology Transfer Office.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
A Commercial License Agreement from the Donor is required for for-profit entities to use this strain. For more information, please contact Technology Transfer Office
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.
4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.