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Vol. 18, Issue 7, 2525-2532, July 2007

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A Knockout Mouse Approach Reveals that TCTP Functions as an Essential Factor for Cell Proliferation and Survival in a Tissue- or Cell Type–specific Manner

Sung Ho Chen^*,, Peih-Shan Wu^,, Chiang-Hung Chou^*, Yu-Ting Yan, Hsuan Liu^*, Shih-Yen Weng^||, and Hsin-Fang Yang-Yen^*,,||

Institutes of *Molecular Biology and Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan; and ^||Institute of Molecular Medicine, National Taiwan University Medical School, Taipei 100, Taiwan

Submitted March 1, 2007; Revised April 11, 2007; Accepted April 23, 2007
Monitoring Editor: Ben Margolis

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.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

These authors contributed equally to this work.

Address correspondence to: Hsin-Fang Yang-Yen (imbyy{at}gate.sinica.edu.tw).

Abbreviations used: TCTP, translationally controlled tumor protein; Shh, Sonic hedgehog; MEF, mouse embryonic fibroblasts.

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