Strain Name:

B6.129S6-Ptpn11tm1Toa/Mmjax

Availability:

Cryopreserved - Ready for recovery     Available at the JAX MMRRC

Please refer to the Mutant Mouse Regional Resource Center (MMRRC) for information about B6.129S6-Ptpn11tm1Toa/Mmjax MMRRC Stock Number 032103.
These mutant mice possess a loxP-STOP-loxP cassette between exons 2 and 3 and a D61Y point mutation in exon 3 of the protein tyrosine phosphatase, non-receptor type 11 (Ptpn11) gene and may be useful in generating conditional mutations to study cardiac defects, fatal myeloproliferative disorder (MPD) and juvenile myelomonocytic leukemia (JMML).

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.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation?pN1
Generation Definitions
 
Donating Investigator Benjamin Neel,   Ontario Cancer Institute

Description
Mice that are homozygous for the targeted mutation are not viable. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. This mutant mouse strain may be useful in generating conditional mutations to study cardiac defects, fatal myeloproliferative disorder (MPD) and juvenile myelomonocytic leukemia (JMML).

When bred to a strain expressing Cre recombinase in endothelial cells (Tg(Tek-cre)12Flv), this mutant mouse strain may be useful in studies of the cardiac defects found in Noonan syndrome.

When bred to a strain expressing Cre recombinase in epiblast-derived tissues (Meox2tm1(cre)Sor), this mutant mouse strain may be useful in studies of cardiac defects.

When bred to a strain expressing tamoxifen-inducible Cre recombinase in most tissues (Tg(CAG-cre/Esr1*)5Amc), this mutant mouse strain may be useful in studies of hematopoiesis.

When bred to a strain expressing interferon-inducible Cre recombinase in most tissues (Tg(Mx1-cre)1Cgn), this mutant mouse strain may be useful in studies of fatal myeloproliferative disorder and juvenile myelomonocytic leukemia (JMML).

When bred to a strain expressing Cre recombinase in neural tube, spinal cord and areas of the brain (Tg(Wnt1-cre)11Rth), this mutant mouse strain may be useful in studies of craniofacial defects.

When bred to a strain expressing Cre recombinase in the early mouse embryo (Tg(EIIa-cre)C5379Lmgd), this mutant mouse strain may be useful in studies of myeloproliferative disorders.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector was designed to place a loxP-neo-loxP-STOP-loxP cassette between exons 2 and 3 and to insert a D61Y point mutation and unique AgeI restriction enzyme site in exon 3 of the targeted gene. The construct was electroporated into 129S6/SvEvTac derived W4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice for a minimum of 10 generations. Upon arrival, mice were bred to C57LB/6J for at least 1 generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ptpn11
012591   B6.129S4-Ptpn11tm1Yan/Mmjax
012593   B6;129S4-Ptpn11tm1Bgn/Mmjax
025758   FVB.129P2(Cg)-Ptpn11tm1.1Wbm/J
View Strains carrying other alleles of Ptpn11     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Juvenile Myelomonocytic Leukemia; JMML   (PTPN11)
Leopard Syndrome 1   (PTPN11)
Metachondromatosis; METCDS   (PTPN11)
Noonan Syndrome 1; NS1   (PTPN11)
View Research Applications

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

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ptpn11tm1Toa
Allele Name targeted mutation 1, Toshiyuki Araki
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Ptpn11inD61Y; inDY;
Mutation Made By Benjamin Neel,   Ontario Cancer Institute
Strain of Origin129S6/SvEvTac
Gene Symbol and Name Ptpn11, protein tyrosine phosphatase, non-receptor type 11
Chromosome 5
Gene Common Name(s) 2700084A17Rik; AW536184; BPTP3; CFC; NS1; PTP-1D; PTP1D; PTP2C; RIKEN cDNA 2700084A17 gene; SH-PTP2; SH-PTP3; SH2 domain-containing protein tyrosine phosphatase-2; SHP-2; SHP2; Syp; expressed sequence AW536184;
Molecular Note A cassette consisting of a loxP site, neo, loxP site, stop signal, and a third loxP site was inserted into intron 2 and a D61Y mutation was inserted into exon 3 via homologous recombination. [MGI Ref ID J:147154] [MGI Ref ID J:148430]

Genotyping

Genotyping Information

Genotyping Protocols

Ptpn11 (exon 3), Sanger sequencing


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Chan G; Kalaitzidis D; Usenko T; Kutok JL; Yang W; Mohi MG; Neel BG. 2009. Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis. Blood 113(18):4414-24. [PubMed: 19179468]  [MGI Ref ID J:148430]

Additional References

Ptpn11tm1Toa related

Araki T; Chan G; Newbigging S; Morikawa L; Bronson RT; Neel BG. 2009. Noonan syndrome cardiac defects are caused by PTPN11 acting in endocardium to enhance endocardial-mesenchymal transformation. Proc Natl Acad Sci U S A 106(12):4736-41. [PubMed: 19251646]  [MGI Ref ID J:147154]

Goodwin CB; Li XJ; Mali RS; Chan G; Kang M; Liu Z; Vanhaesebroeck B; Neel BG; Loh ML; Lannutti BJ; Kapur R; Chan RJ. 2014. PI3K p110delta uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML. Blood 123(18):2838-42. [PubMed: 24553178]  [MGI Ref ID J:210890]

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 & HusbandryWhile maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.

Pricing and Purchasing

Supply Notes


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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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