Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation +pN1 Generation Definitions   Donating Investigator Melvin Simon,   University of California, San Diego

Description
Phospholipase C, beta 3, is critical to G protein-coupled receptor signal transduction pathways regulating mast cell activation and cell migration, as well as intracellular calcium ion release. These mice carry a targeted mutation in which a NEO selection cassette replaced exon 1, encoding the X box of the catalytic domain. Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (mRNA or protein) is detected by Western blot analysis of dorsal root ganglion neurons and neutrophils. Homozygotes exhibit a 5-fold increased sensitivity to morphine, and increased sensitivity to a mu opioid agonist. In reponse to somatostatin, there is no influx of calcium into in aortic smooth muscle cells of homozygotes. Homozygotes 6 months or older sometimes develop skin ulcers around the head area, with infiltration of leukocytes in to the lesions. Histamine, selective H1 histamine receptor agonist, and mast cell activator challenges do not elicit scratching behavior in null mice. Dorsal root ganglion neurons isolated from homozygotes exhibit a decreased calcium response to histamine. Complement 5a induced calcium ion efflux in peritoneal macrophages from homozygotes is decreased when compared to the response in control animals. After thioglycollate treatment, homozygotes exhibit an increase in macrophage apoptosis, resulting in fewer peritoneal macrophages. Macrophages from null mice are hypersensitive to apoptosis inducers such as oxysterol and LPS/cycloheximide. Chemotactic response to antigen of IgE-sensitized bone marrow cells (isolated from homozygotes) is reduced. Bone marrow cells from homozygotes produce less IL-6, TNF-alpha, and IL-13, and exhibit increased Lyn kinase activity.

Development
A targeting vector containing NEO cassette was used to disrupt part of the exon encoding the X box of the catalytic domain. The construct was electroporated into unspecified embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for 5 generations. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Plcb3^tm1Dwu/Plcb3^tm1Dwu

        involves: CD-1

• behavior/neurological phenotype
• analgesia
  • mutants are more sensitive to antinociceptive effects of morphine than wild-type mice   (MGI Ref ID J:57478)
  • mutants show a 5-fold increased sensitivity to morphine as measured by antinociception in hot plate tail-flick assay   (MGI Ref ID J:57478)
• homeostasis/metabolism phenotype
• abnormal calcium ion homeostasis
  • in response to somatostatin, there is no influx of calcium measured in aortic smooth muscle cells in mutants compared to wild-type cells which show show an increased calcium level   (MGI Ref ID J:66819)
• integument phenotype
• analgesia
  • mutants are more sensitive to antinociceptive effects of morphine than wild-type mice   (MGI Ref ID J:57478)
  • mutants show a 5-fold increased sensitivity to morphine as measured by antinociception in hot plate tail-flick assay   (MGI Ref ID J:57478)

Plcb3^tm1Dwu/Plcb3^tm1Dwu

        Background Not Specified

• integument phenotype
• spontaneous skin ulceration
  • at 6 months or older behind the ears, on the next, or sometimes on the face   (MGI Ref ID J:60348)

View Research Applications

Research Applications

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

Apoptosis Research

Cell Biology Research
Channel and Transporter Defects
      calcium

Hematological Research
Mast Cell Deficiency

Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
      Mast Cell Deficiency

Neurobiology Research
Behavioral and Learning Defects
      mu opioid receptor deficiency
Channel and Transporter Defects
      calcium

Research Tools
Apoptosis Research
Immunology and Inflammation Research
      Mast Cell Deficiency

Sensorineural Research
Nociception

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Plcb3tm1Dwu
Allele Name		targeted mutation 1, Dianqing Wu
Allele Type		Targeted (knock-out)
Common Name(s)		PLC beta3-null;
Mutation Made By		Estelle Wall,   University of California, San Diego
Gene Symbol and Name		Plcb3, phospholipase C, beta 3
Chromosome		19
Molecular Note		A neomycin selection cassette replaced part of the exon encoding the X box. Western blot analysis demonstrated that no detectable protein was present in homogenates of dorsal root ganglia derived from homozygous mice. [MGI Ref ID J:57478]

Genotyping

Genotyping Information

Genotyping Protocols

Plcb3^tm1Dwu,

Separated MCA

Plcb4^tm1Dwualternate2, Separated PCR
Plcb3^tm1Dwu, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Xie W; Samoriski GM; McLaughlin JP; Romoser VA; Smrcka A; Hinkle PM; Bidlack JM; Gross RA; Jiang H; Wu D. 1999. Genetic alteration of phospholipase C beta3 expression modulates behavioral and cellular responses to mu opioids. Proc Natl Acad Sci U S A 96(18):10385-90. [PubMed: 10468617]  [MGI Ref ID J:57478]

Additional References

Plcb3^tm1Dwu related

Han SK; Mancino V; Simon MI. 2006. Phospholipase Cbeta 3 mediates the scratching response activated by the histamine H1 receptor on C-fiber nociceptive neurons. Neuron 52(4):691-703. [PubMed: 17114052]  [MGI Ref ID J:122931]

Hoeppner LH; Phoenix KN; Clark KJ; Bhattacharya R; Gong X; Sciuto TE; Vohra P; Suresh S; Bhattacharya S; Dvorak AM; Ekker SC; Dvorak HF; Claffey KP; Mukhopadhyay D. 2012. Revealing the role of phospholipase Cbeta3 in the regulation of VEGF-induced vascular permeability. Blood 120(11):2167-73. [PubMed: 22674805]  [MGI Ref ID J:189097]

Imamachi N; Park GH; Lee H; Anderson DJ; Simon MI; Basbaum AI; Han SK. 2009. TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proc Natl Acad Sci U S A 106(27):11330-5. [PubMed: 19564617]  [MGI Ref ID J:150810]

Li Z; Jiang H; Xie W; Zhang Z; Smrcka AV; Wu D. 2000. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction [see comments] Science 287(5455):1046-9. [PubMed: 10669417]  [MGI Ref ID J:60348]

Lian L; Wang Y; Draznin J; Eslin D; Bennett JS; Poncz M; Wu D; Abrams CS. 2005. The relative role of PLCbeta and PI3Kgamma in platelet activation. Blood 106(1):110-7. [PubMed: 15705797]  [MGI Ref ID J:107460]

Romoser VA; Graves TK; Wu D; Jiang H; Hinkle PM. 2001. Calcium responses to thyrotropin-releasing hormone, gonadotropin-releasing hormone and somatostatin in phospholipase css3 knockout mice. Mol Endocrinol 15(1):125-35. [PubMed: 11145744]  [MGI Ref ID J:66819]

Suire S; Lecureuil C; Anderson KE; Damoulakis G; Niewczas I; Davidson K; Guillou H; Pan D; Clark J; Hawkins PT; Stephens L. 2012. GPCR activation of Ras and PI3Kgamma in neutrophils depends on PLCbeta2/beta3 and the RasGEF RasGRP4. EMBO J :. [PubMed: 22728827]  [MGI Ref ID J:186412]

Wang Z; Liu B; Wang P; Dong X; Fernandez-Hernando C; Li Z; Hla T; Li Z; Claffey K; Smith JD; Wu D. 2008. Phospholipase C beta3 deficiency leads to macrophage hypersensitivity to apoptotic induction and reduction of atherosclerosis in mice. J Clin Invest 118(1):195-204. [PubMed: 18079968]  [MGI Ref ID J:130826]

Xiao W; Ando T; Wang HY; Kawakami Y; Kawakami T. 2010. Lyn- and PLC-beta3-dependent regulation of SHP-1 phosphorylation controls Stat5 activity and myelomonocytic leukemia-like disease. Blood 116(26):6003-13. [PubMed: 20858858]  [MGI Ref ID J:167395]

Xiao W; Hong H; Kawakami Y; Kato Y; Wu D; Yasudo H; Kimura A; Kubagawa H; Bertoli LF; Davis RS; Chau LA; Madrenas J; Hsia CC; Xenocostas A; Kipps TJ; Hennighausen L; Iwama A; Nakauchi H; Kawakami T. 2009. Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5. Cancer Cell 16(2):161-71. [PubMed: 19647226]  [MGI Ref ID J:151972]

Xiao W; Kashiwakura J; Hong H; Yasudo H; Ando T; Maeda-Yamamoto M; Wu D; Kawakami Y; Kawakami T. 2011. Phospholipase C-beta3 Regulates FcvarepsilonRI-Mediated Mast Cell Activation by Recruiting the Protein Phosphatase SHP-1. Immunity 34(6):893-904. [PubMed: 21683628]  [MGI Ref ID J:174006]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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