Description

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x Heterozygote         (Female x Male)   14-SEP-12 Species laboratory mouse Generation ?+N1F (08-NOV-12) Generation Definitions   Donating Investigator Iannis Aifantis,   NYU School of Medicine

Description
Like TET1 and TET3, TET2 modifies DNA by hydroxylating 5 methylcytosine. A significant percentage of patients with myeloid malignancies exhibit mutations in TET2, of these, 41.5% of mutations occur in the first coding exon (mouse exon 3). These Tet2^f/f mice possess loxP sites flanking exon 3. Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. 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 hematopoietic stem cell self-renewal and myeloid transformation.

For example, when crossed to a strain expressing interferon-inducible Cre recombinase (see Stock No. 003556), mice exhibit increased hematopoietic stem cell self-renewal.

Development
A targeting vector was designed to place an FRT- and loxP-flanked neomycin resistance cassette upstream of exon 3 and a loxP site downstream of exon 3. The construct was electroporated into BAC-BA1(129S/SvEV x C57BL/6)-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. Strong chimeras were identified and crossed to C57BL/6 females to verify germline transmission. The F1 generation was PCR screened and crossed to 129S4/SvJaeSor-Gt(ROSA)26Sor^tm1(FLP1)Dym/J (JR#003946) to remove the FRT neo cassette.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls

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. Myelodysplastic Syndrome; MDS   (TET2)

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.
Contact JAX^® Services jaxservices@jax.org for customized breeding options.

Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(EIIa-cre)C5379Lmgd/0

        involves: 129S/SvEv * C57BL/6 * FVB/N   (conditional)

• normal phenotype
• no abnormal phenotype detected
  • mice are born with at the expected Mendelian ratio with normal growth and organ development   (MGI Ref ID J:174053)

Tet2^tm1.1Iaai/Tet2^tm1.1Iaai Tg(Mx1-cre)1Cgn/0

        involves: 129S/SvEv * C57BL/6 * CBA   (conditional)

• hematopoietic system phenotype
• abnormal hematopoietic stem cell physiology
  • in transplantation experiments, pIpC-treated hematopoietic stem cells exhibit increased self-renewal compared with control cells   (MGI Ref ID J:174053)

View Research Applications

Research Applications

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

Research Tools
Cancer Research
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tet2tm1.1Iaai
Allele Name		targeted mutation 1.1, Iannis Aifantis
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		Tet2f;
Mutation Made By		Iannis Aifantis,   NYU School of Medicine
Strain of Origin		C57BL/6 x 129S/SvEv
Gene Symbol and Name		Tet2, tet methylcytosine dioxygenase 2
Chromosome		3
Gene Common Name(s)		Ayu17-449; E130014J05Rik; KIAA1546; MDS; RIKEN cDNA E130014J05 gene; mKIAA1546;
General Note		ES cell = BAC-BA1 (C57BL/6 x 129S/SvEv)
Molecular Note		An FRT- and loxP-flanked neo cassette was inserted upstream of exon 3. An additional loxP site was inserted downstream of exon 3. Flp-mediated recombination removed the neo cassette and left exon 3 floxed. [MGI Ref ID J:174053]

Genotyping

Genotyping Information

Genotyping Protocols

Tet2^tm1.1Iaai, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Moran-Crusio K; Reavie L; Shih A; Abdel-Wahab O; Ndiaye-Lobry D; Lobry C; Figueroa ME; Vasanthakumar A; Patel J; Zhao X; Perna F; Pandey S; Madzo J; Song C; Dai Q; He C; Ibrahim S; Beran M; Zavadil J; Nimer SD; Melnick A; Godley LA; Aifantis I; Levine RL. 2011. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20(1):11-24. [PubMed: 21723200]  [MGI Ref ID J:174053]

Additional References

Tet2^tm1.1Iaai related

Deplus R; Delatte B; Schwinn MK; Defrance M; Mendez J; Murphy N; Dawson MA; Volkmar M; Putmans P; Calonne E; Shih AH; Levine RL; Bernard O; Mercher T; Solary E; Urh M; Daniels DL; Fuks F. 2013. TET2 and TET3 regulate GlcNAcylation and H3K4 methylation through OGT and SET1/COMPASS. EMBO J 32(5):645-55. [PubMed: 23353889]  [MGI Ref ID J:194478]

Doege CA; Inoue K; Yamashita T; Rhee DB; Travis S; Fujita R; Guarnieri P; Bhagat G; Vanti WB; Shih A; Levine RL; Nik S; Chen EI; Abeliovich A. 2012. Early-stage epigenetic modification during somatic cell reprogramming by Parp1 and Tet2. Nature 488(7413):652-5. [PubMed: 22902501]  [MGI Ref ID J:187148]

Kallin EM; Rodriguez-Ubreva J; Christensen J; Cimmino L; Aifantis I; Helin K; Ballestar E; Graf T. 2012. Tet2 facilitates the derepression of myeloid target genes during CEBPalpha-induced transdifferentiation of pre-B cells. Mol Cell 48(2):266-76. [PubMed: 22981865]  [MGI Ref ID J:191279]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.
Mating System	Heterozygote x Heterozygote         (Female x Male)   14-SEP-12
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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