Strain Detail Sheet

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

Strain Information

Gene Details

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: cn, guanylyl cyclase-B, pwe
Type: Gene
Species: Mouse
Chromosome: 4
Alteration at locus: Knock-In
NCBI: 230103
HGNC: HGNC:7944
Homologene: 2970
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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).

Genotype Determination
ES Cell Line
129Sv derived from 129S2/SvPas

Strain Description

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

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.

Research Applications

  • Cardiovascular
  • Cell Biology
  • Developmental Biology
  • Endocrine Deficiency
  • Models for Human Disease
  • Neurobiology
  • Reproduction

Strain Origin

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

Special Considerations

N/A

Health Status Report

For more information about this colony's health status contact csmmrrc@jax.org

Appearance

Coat Color
Agouti
Eye
Black

Breeding

MMRRC Breeding System
Sib-mating
Generation
N>5
Overall Breeding Performance
Excellent

Reproductive Statistics

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

Availability Level

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.

Conditions of Distribution

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.

The donor or their institution limits the distribution to non-profit institutions only.

Fees

- Products for this strain are Not Yet Available for Ordering
- If you register interest in this strain, you will be notified when it becomes available for ordering.
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.