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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Yuan Zhuang,   Duke University Medical Center

Description
A targeting vector was designed to replace the C-terminus DNA-binding domain of transcription factor 4 (Tcf4 or E2-2) gene with a neomycin (neo) selection cassette. Homozygotes are born at a low frequency and die within the first week of life. E2-2 is a widely expressed E2A-related helix-loop-helix (HLH) protein required for the generation of normal numbers of pro-B cells in mouse embryos. While homozygous E2-2 mutant embryos are capable of making B cells, they produce only half as many as wildtype. When crossed to mice containing a (Atoh1)-lacZ transgene, β-galactosidase staining is evident in anterior extramural migratory stream (AES) cells which accumulate in the region lateral to the pontine nucleus. The resulting mice exhibit a reduction in size of the pontine nucleus and a lack of migration of neuronal precursors to the region of the pontine nucleus. Mice heterozygous for the mutation are viable, fertile, and normal in size. This strain may be useful for studying B cell development, activation of differentiation of a subset of neural progenitors, and neurodevelopment associated with Pitt-Hopkins syndrome (PHS).

Development
A targeting vector was designed to replace the C-terminus DNA-binding domain of transcription factor 4 (Tcf4 or E2-2) gene with a neomycin (neo) selection cassette. This construct was electroporated into 129P2/OlaHsd-derived EFC-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with C57BL/6 mice and were maintained as a mixed C57BL/6 x 129/Sv colony. Upon arrival at The Jackson Laboratory, these mice were bred with B6129SF1/J mice (Stock No. 101043) for at least one generation to establish the colony.

Control Information

	Control
	Wild-type from the colony
	100903 B6129PF2/J	(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. Pitt-Hopkins Syndrome; PTHS   (TCF4)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Tcf4^tm1Zhu/Tcf4^tm1Zhu

        involves: 129P2/OlaHsd * C57BL/6

• mortality/aging
• complete postnatal lethality
  • homozygotes born with low frequency and died within one week of birth   (MGI Ref ID J:43324)
• hematopoietic system phenotype
• decreased pro-B cell number
  • 50% reduction in the number of pro-B cells in homozygotes   (MGI Ref ID J:43324)
• immune system phenotype
• decreased pro-B cell number
  • 50% reduction in the number of pro-B cells in homozygotes   (MGI Ref ID J:43324)
• cellular phenotype
• decreased pro-B cell number
  • 50% reduction in the number of pro-B cells in homozygotes   (MGI Ref ID J:43324)

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

Tcf4^tm1Zhu/Tcf4^tm1Zhu

        involves: 129P2/OlaHsd

• mortality/aging
• complete neonatal lethality
  • mice die within the first 24 hours of birth but no embryonic lethality is observed as previously noted   (MGI Ref ID J:125313)
• nervous system phenotype
• abnormal brain development
  • the pontine nuclei is disrupted   (MGI Ref ID J:125313)

View Research Applications

Research Applications

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

Developmental Biology Research
Neurodevelopmental Defects
Postnatal Lethality
      Homozygous

Research Tools
Cancer Research
      B cell deficiency

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tcf4tm1Zhu
Allele Name		targeted mutation 1, Yuan Zhuang
Allele Type		Targeted (knock-out)
Common Name(s)		E2-2-; Tcf4-;
Mutation Made By		Yuan Zhuang,   Duke University Medical Center
Strain of Origin		129P2/OlaHsd
Gene Symbol and Name		Tcf4, transcription factor 4
Chromosome		18
Gene Common Name(s)		5730422P05Rik; ASP-I2; E2-2; E2.2; ITF-2; ITF-2b; ITF2; ME2; MITF-2A; MITF-2B; PTHS; RIKEN cDNA 5730422P05 gene; SEF-2; SEF2; SEF2-1; SEF2-1A; SEF2-1B; TCF-4; TFE; Tcf-4; bHLHb19;
General Note		ES cell line = EFC-1.
Molecular Note		The insertion of a neomycin selection cassette deleted sequence encoding the carboxy terminal, including a portion of the basic helix-loop-helix (bHLH) domain. The disruption of the bHLH precludes dimerization, thereby preventing the potential for DNA binding activity. [MGI Ref ID J:43324]

Genotyping

Genotyping Information

Genotyping Protocols

Tcf4^tm1Zhu,

Separated MCA

Atoh^tm2Hzo,

Separated MCA

Atoh^tm2Hzo, Separated PCR
Tcf4^tm1Zhu, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Zhuang Y; Cheng P; Weintraub H. 1996. B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2, and HEB. Mol Cell Biol 16(6):2898-905. [PubMed: 8649400]  [MGI Ref ID J:43324]

Additional References

Tcf4^tm1Zhu related

Bar-On L; Birnberg T; Lewis KL; Edelson BT; Bruder D; Hildner K; Buer J; Murphy KM; Reizis B; Jung S. 2010. CX3CR1+ CD8alpha+ dendritic cells are a steady-state population related to plasmacytoid dendritic cells. Proc Natl Acad Sci U S A 107(33):14745-50. [PubMed: 20679228]  [MGI Ref ID J:163703]

Bergqvist I; Eriksson M; Saarikettu J; Eriksson B; Corneliussen B; Grundstrom T; Holmberg D. 2000. The basic helix-loop-helix transcription factor E2-2 is involved in T lymphocyte development Eur J Immunol 30(10):2857-63. [PubMed: 11069067]  [MGI Ref ID J:65236]

Cervantes-Barragan L; Lewis KL; Firner S; Thiel V; Hugues S; Reith W; Ludewig B; Reizis B. 2012. Plasmacytoid dendritic cells control T-cell response to chronic viral infection. Proc Natl Acad Sci U S A 109(8):3012-7. [PubMed: 22315415]  [MGI Ref ID J:182008]

Cisse B; Caton ML; Lehner M; Maeda T; Scheu S; Locksley R; Holmberg D; Zweier C; den Hollander NS; Kant SG; Holter W; Rauch A; Zhuang Y; Reizis B. 2008. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135(1):37-48. [PubMed: 18854153]  [MGI Ref ID J:147515]

Flora A; Garcia JJ; Thaller C; Zoghbi HY. 2007. The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. Proc Natl Acad Sci U S A 104(39):15382-7. [PubMed: 17878293]  [MGI Ref ID J:125313]

Ghosh HS; Cisse B; Bunin A; Lewis KL; Reizis B. 2010. Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity 33(6):905-16. [PubMed: 21145760]  [MGI Ref ID J:167292]

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, heterozygous mice may be bred to wildtype mice from the colony or B6129SF2/J mice (Stock No. 101043).

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
	100903 B6129PF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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