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Strain Name:
B6;129S-Npr2tm1.2Laj/Mmjax
Stock Number:
071310-JAX
Citation ID:
RRID:MMRRC_071310-JAX
Other Names:
Npr2-7E-cKI

Strain Information

Npr2tm1.2Laj
Name: natriuretic peptide receptor 2; targeted mutation 1.2, Laurinda A Jaffe
Synonyms: Npr2-7E cKI
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 4
Alteration at locus: Knock-In
Npr2
Name: natriuretic peptide receptor 2
Synonyms: guanylyl cyclase-B, cn, pwe
Type: Gene
Species: Mouse
Chromosome: 4
Alteration at locus: Knock-In
NCBI: 230103
HGNC: HGNC:7944
Homologene: 2970
Genetic Alterations

Conditional Npr2-7E cKI mice have a loxP-flanked EGFP reporter upstream of 7 glutamate substitutions (7E) in exons 8 and 9 of the Npr2 (natriuretic peptide receptor 2) gene. The 7E mutations prevent NPR2 dephosphorylation and inactivation. These floxed mice may be used as a tool for understanding signaling in mouse preovulatory follicles and bone growth regulation.

Of note, mice constitutively expressing the 7E mutations are available as B6;129-Npr2tm1.2Laj/Mmjax (MMRRC Stock No. 071312).

ES Cell Line
129Sv derived from 129S2/SvPas
Phenotype
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.

Conditional Npr2-7E cKI mice contain loxP sites flanking a wild-type Npr2 sequence, an EGFP reporter inserted into intron 7, followed by 7 glutamate substitutions in exons 8 and 9 of the Npr2 gene. The 7E point mutations are located in the juxtamembrane 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. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will constitutively express the 7E mutations in the cre-expressing tissues resulting in a tissue specific mutant allele.

When combined with mice carrying widespread expression of Cre recombinase (Hprttm1(CAG-cre)Mnn), female progeny have a delayed resumption of meiosis in response to luteinizing hormone. In addition, progeny develop longer and stronger bones.

Of note, mice constitutively expressing the 7E mutations are available as B6;129-Npr2tm1.2Laj/Mmjax (MMRRC Stock No. 071312).
MeSH Terms
  • Animals
  • Cyclic GMP/metabolism
  • Epiregulin/pharmacology
  • Female
  • Granulosa Cells/drug effects
  • Granulosa Cells/metabolism
  • Guanylate Cyclase/metabolism
  • Luteinizing Hormone/pharmacology
  • Meiosis/drug effects
  • Mice
  • Oocytes/cytology
  • Oocytes/enzymology
  • Phosphorylation/drug effects
  • Receptors, Atrial Natriuretic Factor/metabolism
  • Serine/metabolism
  • Sheep
  • Threonine/metabolism
Strain Development

The Npr2-7E-cKI targeting vector was designed to insert a loxP site, a wild-type Npr2 minigene 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 insert 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 B6.129S4-Gt(ROSA)26Sortm1(FLP1)Dym/J females to remove the neomycin cassette. The flp allele was later bred out of the strain. The 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.

Suggested Control Mice
C57BL/6J
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Endocrine Deficiency
  • Models for Human Disease
  • Neurobiology
  • Reproduction
Donor
Laurinda Jaffe, Ph.D., University of Connecticut Health Center.
Primary Reference

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)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.
Coat Color
Agouti
Eye
Black
MMRRC Breeding System
Sib-mating
Generation
N>5
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Heterozygotes are fertile: Yes Yes
Age Reproductive Decline: Undetermined Undetermined
Average litter size
Variable
Recommended wean age
3 Weeks
Average Pups Weaned
Variable

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

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.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
071310-JAX-SPERM Cryo-preserved spermatozoa $459.00 / $459.00
Non-Profit / For-Profit
Aliquot Approximate quantity3
071310-JAX-RESUS Litter recovered from cryo-archive $2,123.00 / $2,123.00
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

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.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.