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Updated: Jul 15, 2026

Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
A knockout mouse approach reveals that TCTP functions as an essential factor for cell proliferation and survival in a
Sung Ho Chen1, Peih-Shan Wu, Chiang-Hung Chou
1Institutes of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Abstract:
Translationally controlled Tumor Protein (TCTP) is an evolutionally highly conserved protein which has been implicated in many cellular functions that are related to cell growth, death, and even the allergic response of the host. To address the physiological roles of TCTP, we generated TCTP knockout mice by targeted gene disruption. Heterozygous mutants appeared to be developmentally normal. However, homozygous mutants (TCTP(-/-)) were embryonic lethal. TCTP(-/-) embryos were smaller in size than the control littermates at all postimplantation stages examined. Although TCTP is widely expressed in both extraembryonic and embryonic tissues, the most prominent defect of the TCTP(-/-) embryo at embryonic stage day 5.5 (E5.5) was in its epiblast, which had a reduced number of cells compared with wild-type controls. The knockout embryos also suffered a higher incidence of apoptosis in epiblast starting about E6.5 and subsequently died around E9.5-10.5 with a severely disorganized structure. Last, we demonstrated that TCTP(-/-) and control mouse embryonic fibroblasts manifested similar proliferation activities and apoptotic sensitivities to various death stimuli. Taken together, our results suggest that despite that TCTP is widely expressed in many tissues or cell types, it appears to regulate cell proliferation and survival in a tissue- or cell type-specific manner.
Insights
Translationally controlled Tumor Protein (TCTP) is essential for embryonic development. TCTP knockout mice show embryonic lethality due to defects in epiblast cell number and increased apoptosis.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Translationally controlled Tumor Protein (TCTP) is a highly conserved protein involved in cell growth, death, and allergic responses.
- Its precise physiological roles, particularly during embryonic development, remain incompletely understood.
Purpose of the Study:
- To investigate the essential physiological roles of TCTP during mouse embryonic development using a gene knockout approach.
Main Methods:
- Generation of TCTP knockout mice via targeted gene disruption.
- Analysis of embryonic development, morphology, cell proliferation, and apoptosis in homozygous TCTP(-/-) embryos.
- Comparison of TCTP(-/-) and wild-type mouse embryonic fibroblasts (MEFs) for proliferation and apoptotic sensitivity.
Main Results:
- Homozygous TCTP(-/-) mice exhibit embryonic lethality, with smaller embryos and reduced epiblast cell numbers at E5.5.
- TCTP(-/-) embryos display increased apoptosis in the epiblast from E6.5 and die around E9.5-10.5 with severe structural disorganization.
- TCTP(-/-) and wild-type MEFs show similar proliferation rates and apoptotic sensitivities, indicating tissue-specific roles.
Conclusions:
- TCTP is crucial for embryonic development, particularly for epiblast cell survival and proliferation.
- TCTP's function in regulating cell proliferation and survival appears to be tissue- or cell type-specific.
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