Homozygotes for this knockout mutation of the Tcf4 gene are born at a low frequency and die within the first week of life. When still viable, mice have a diminished capacity to generate B cells.
Yuan Zhuang, Duke University Medical Center
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).
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.
|Allele Name||targeted mutation 1, Yuan Zhuang|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||E2-2-; Tcf4-|
|Gene Symbol and Name||Tcf4, transcription factor 4|
|Gene Synonym(s)||5730422P05Rik; 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; SEF2-1D; TCF-4; TFE; Tcf-4; bHLHb19|
|Strain of Origin||129P2/OlaHsd|
|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.|
|Mutations Made By|| |
Yuan Zhuang, Duke University Medical Center
When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or B6129SF2/J mice (Stock No. 101043).
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