Strain Name:

B6;129S-Ppp3r1tm2Grc/J

Stock Number:

017692

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Availability:

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Use Restrictions Apply, see Terms of Use
This strain carries a floxed allele of the Ppp3r1 gene. Cre excision disrupts calcineurin enzymatic activity in non-germline cell types. These mice have been useful in studies of T cell development/selection.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHomozygote x Homozygote         (Female x Male)   06-DEC-12
Specieslaboratory mouse
GenerationF?+f4 (02-MAY-12)
Generation Definitions
 
Donating Investigator Gerald R Crabtree,   Stanford University Medical Center

Description
LoxP sites flank exons 3-5 of the Calcineurin β1 (Ppp3r1, protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I)) gene in these floxed mutant mice. When bred to Cre-recombinase mice, excision of the floxed exons can be directed in a tissue/cell-specific manner in the resulting offspring. Disruption of the calcineurin β1 subunit results in a lack of calcineurin enzymatic activity in non-germline cell types. Ppp3r1 is a Ca2+-binding regulatory subunit of heterodimeric calcineurin, a Ca2+- and calmodulin-dependent serine/threonine protein phosphatase involved in a number of cellular processes and calcium-dependent signaling pathways.

When crossed with Lck-cre mice to specifically block calcineurin expression in thymocytes, it was shown that calcineurin β1 is essential for positive but not negative selection during thymocyte development.

When bred to a strain expressing Cre recombinase in endothelial cells (see Stock No. 008863 for example), this mutant mouse strain may be useful in studies of angiogenesis.

Development
Exons 3-5 of the targeted gene were flanked by loxP sites and an FRT-flanked neomycin cassette was introduced to intron 3 using TC1 129S6/SvEvTac-derived embryonic stem (ES) cells. Transient transfection with a FLP-expressing vector excised the neomycin cassette. This strain was backcrossed to 129S1/SvImJ and maintained on a mixed C57BL/6-129S genetic background by the donating lab.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ppp3r1
006581   C57BL/6-Ppp3r1tm1Stl/J
View Strains carrying other alleles of Ppp3r1     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype relates to a compound genotype created using this strain.
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Ppp3r1tm2Grc/Ppp3r1tm2Grc Tg(Tagln-cre)1Her/0

        involves: 129S6/SvEvTac * C57BL/6 * SJL   (conditional)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • mice are grossly normal and display normal coronary endothelial patterning at E12.5; mice live to adulthood and are indistinguishable from wild-type littermates   (MGI Ref ID J:153636)

Ppp3r1tm2Grc/Ppp3r1tm2Grc Tg(Tek-cre)1Ywa/0

        involves: 129S6/SvEvTac * C57BL/6 * SJL   (conditional)
  • mortality/aging
  • partial embryonic lethality during organogenesis
    • most embryos die at E13 due to heart valve defects   (MGI Ref ID J:153636)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • peripheral vasculature is not observably different from wild-type at E10.5 and 11.5; cranial, intersomitic and dorsal vessels appear normal at E10.5 and 11.5   (MGI Ref ID J:153636)
    • at E12.5, no significant differences in endothelial cell proliferation or apoptosis are detected   (MGI Ref ID J:153636)
    • abnormal heart development
      • hearts at E12.5 show limited endothelial branching compared to extensive network of endothelial tubes in wild-type   (MGI Ref ID J:153636)
    • abnormal vascular endothelial cell development
      • coronary endothelial cells are fused and limited to the atrioventricular junction; PECAM1-positive endothelial cells are limited to basal portion of ventricles with no cells reaching the apical region of the heart   (MGI Ref ID J:153636)
View Research Applications

Research Applications
This mouse can be used to support research in many areas including:

Cell Biology Research
Signal Transduction

Research Tools
Cell Biology Research
Cre-lox System
      loxP-flanked Sequences
Immunology, Inflammation and Autoimmunity Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ppp3r1tm2Grc
Allele Name targeted mutation 2, Gerald R Crabtree
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) CnB1-LoxP; Cnb1f; Cnb1flox;
Mutation Made By Gerald Crabtree,   Stanford University Medical Center
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Ppp3r1, protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I)
Chromosome 11
Gene Common Name(s) CALNB1; CNB; CNB1; CaNB1; PP2B beta 1;
Molecular Note Exons 3 through 5 were flanked by single loxP sites. A single frt site remained in intron 3 following FLP-mediated excition of an frt-flanked neo cassette. [MGI Ref ID J:89771]

Genotyping

Genotyping Information

Genotyping Protocols

Ppp3r1tm2Grc, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Ppp3r1tm2Grc related

Chang CP; McDill BW; Neilson JR; Joist HE; Epstein JA; Crabtree GR; Chen F. 2004. Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. J Clin Invest 113(7):1051-8. [PubMed: 15057312]  [MGI Ref ID J:89217]

Choo MK; Yeo H; Zayzafoon M. 2009. NFATc1 mediates HDAC-dependent transcriptional repression of osteocalcin expression during osteoblast differentiation. Bone 45(3):579-89. [PubMed: 19463978]  [MGI Ref ID J:154803]

Dave V; Childs T; Xu Y; Ikegami M; Besnard V; Maeda Y; Wert SE; Neilson JR; Crabtree GR; Whitsett JA. 2006. Calcineurin/Nfat signaling is required for perinatal lung maturation and function. J Clin Invest 116(10):2597-609. [PubMed: 16998587]  [MGI Ref ID J:114501]

Gallo EM; Ho L; Winslow MM; Staton TL; Crabtree GR. 2008. Selective role of calcineurin in haematopoiesis and lymphopoiesis. EMBO Rep 9(11):1141-8. [PubMed: 18818667]  [MGI Ref ID J:143345]

Gallo EM; Winslow MM; Cante-Barrett K; Radermacher AN; Ho L; McGinnis L; Iritani B; Neilson JR; Crabtree GR. 2007. Calcineurin sets the bandwidth for discrimination of signals during thymocyte development. Nature 450(7170):731-5. [PubMed: 18046413]  [MGI Ref ID J:130376]

Goodyer WR; Gu X; Liu Y; Bottino R; Crabtree GR; Kim SK. 2012. Neonatal beta cell development in mice and humans is regulated by calcineurin/NFAT. Dev Cell 23(1):21-34. [PubMed: 22814600]  [MGI Ref ID J:187609]

Greenblatt MB; Aliprantis A; Hu B; Glimcher LH. 2010. Calcineurin regulates innate antifungal immunity in neutrophils. J Exp Med 207(5):923-31. [PubMed: 20421389]  [MGI Ref ID J:160937]

Heit JJ; Apelqvist AA; Gu X; Winslow MM; Neilson JR; Crabtree GR; Kim SK. 2006. Calcineurin/NFAT signalling regulates pancreatic beta-cell growth and function. Nature 443(7109):345-9. [PubMed: 16988714]  [MGI Ref ID J:112976]

Kao SC; Wu H; Xie J; Chang CP; Ranish JA; Graef IA; Crabtree GR. 2009. Calcineurin/NFAT signaling is required for neuregulin-regulated Schwann cell differentiation. Science 323(5914):651-4. [PubMed: 19179536]  [MGI Ref ID J:144171]

Lazarevic V; Zullo AJ; Schweitzer MN; Staton TL; Gallo EM; Crabtree GR; Glimcher LH. 2009. The gene encoding early growth response 2, a target of the transcription factor NFAT, is required for the development and maturation of natural killer T cells. Nat Immunol 10(3):306-13. [PubMed: 19169262]  [MGI Ref ID J:146134]

Lin CY; Lin CJ; Chen CH; Chen RM; Zhou B; Chang CP. 2012. The secondary heart field is a new site of calcineurin/Nfatc1 signaling for semilunar valve development. J Mol Cell Cardiol 52(5):1096-102. [PubMed: 22300732]  [MGI Ref ID J:183686]

Maillet M; Davis J; Auger-Messier M; York A; Osinska H; Piquereau J; Lorenz JN; Robbins J; Ventura-Clapier R; Molkentin JD. 2010. Heart-specific deletion of CnB1 reveals multiple mechanisms whereby calcineurin regulates cardiac growth and function. J Biol Chem 285(9):6716-24. [PubMed: 20037164]  [MGI Ref ID J:160029]

Mammucari C; Tommasi di Vignano A; Sharov AA; Neilson J; Havrda MC; Roop DR; Botchkarev VA; Crabtree GR; Dotto GP. 2005. Integration of Notch 1 and calcineurin/NFAT signaling pathways in keratinocyte growth and differentiation control. Dev Cell 8(5):665-76. [PubMed: 15866158]  [MGI Ref ID J:105135]

Neilson JR; Winslow MM; Hur EM; Crabtree GR. 2004. Calcineurin B1 is essential for positive but not negative selection during thymocyte development. Immunity 20(3):255-66. [PubMed: 15030770]  [MGI Ref ID J:89771]

Parsons SA; Millay DP; Sargent MA; Naya FJ; McNally EM; Sweeney HL; Molkentin JD. 2007. Genetic disruption of calcineurin improves skeletal muscle pathology and cardiac disease in a mouse model of limb-girdle muscular dystrophy. J Biol Chem 282(13):10068-78. [PubMed: 17289669]  [MGI Ref ID J:121162]

Parsons SA; Millay DP; Wilkins BJ; Bueno OF; Tsika GL; Neilson JR; Liberatore CM; Yutzey KE; Crabtree GR; Tsika RW; Molkentin JD. 2004. Genetic loss of calcineurin blocks mechanical overload-induced skeletal muscle fiber type switching but not hypertrophy. J Biol Chem 279(25):26192-200. [PubMed: 15082723]  [MGI Ref ID J:91040]

Sanna B; Bueno OF; Dai YS; Wilkins BJ; Molkentin JD. 2005. Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth. Mol Cell Biol 25(3):865-78. [PubMed: 15657416]  [MGI Ref ID J:95999]

Schaeffer PJ; Desantiago J; Yang J; Flagg TP; Kovacs A; Weinheimer CJ; Courtois M; Leone TC; Nichols CG; Bers DM; Kelly DP. 2009. Impaired contractile function and calcium handling in hearts of cardiac-specific calcineurin b1-deficient mice. Am J Physiol Heart Circ Physiol 297(4):H1263-73. [PubMed: 19700627]  [MGI Ref ID J:154326]

Schaeffer PJ; Wende AR; Magee CJ; Neilson JR; Leone TC; Chen F; Kelly DP. 2004. Calcineurin and calcium/calmodulin-dependent protein kinase activate distinct metabolic gene regulatory programs in cardiac muscle. J Biol Chem 279(38):39593-603. [PubMed: 15262994]  [MGI Ref ID J:93357]

Stefater JA 3rd; Rao S; Bezold K; Aplin AC; Nicosia RF; Pollard JW; Ferrara N; Lang RA. 2013. Macrophage Wnt-Calcineurin-Flt1 signaling regulates mouse wound angiogenesis and repair. Blood 121(13):2574-8. [PubMed: 23303818]  [MGI Ref ID J:195441]

Winslow MM; Gallo EM; Neilson JR; Crabtree GR. 2006. The calcineurin phosphatase complex modulates immunogenic B cell responses. Immunity 24(2):141-52. [PubMed: 16473827]  [MGI Ref ID J:113318]

Wu X; Nguyen BC; Dziunycz P; Chang S; Brooks Y; Lefort K; Hofbauer GF; Dotto GP. 2010. Opposing roles for calcineurin and ATF3 in squamous skin cancer. Nature 465(7296):368-72. [PubMed: 20485437]  [MGI Ref ID J:161959]

Yeo H; Beck LH; Thompson SR; Farach-Carson MC; McDonald JM; Clemens TL; Zayzafoon M. 2007. Conditional disruption of calcineurin B1 in osteoblasts increases bone formation and reduces bone resorption. J Biol Chem 282(48):35318-27. [PubMed: 17884821]  [MGI Ref ID J:129000]

Zeini M; Hang CT; Lehrer-Graiwer J; Dao T; Zhou B; Chang CP. 2009. Spatial and temporal regulation of coronary vessel formation by calcineurin-NFAT signaling. Development 136(19):3335-45. [PubMed: 19710169]  [MGI Ref ID J:153636]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryHomozygotes or heterozygotes may be bred.
Mating SystemHomozygote x Homozygote         (Female x Male)   06-DEC-12
Diet Information LabDiet® 5K20

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Ppp3r1tm2Grc  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Ppp3r1tm2Grc x Homozygous for Ppp3r1tm2Grc  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Ppp3r1tm2Grc  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Ppp3r1tm2Grc x Homozygous for Ppp3r1tm2Grc  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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