title: 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.
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.
authors.affiliation: Institutes of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Chen
authors.forename: Peih-Shan
authors.initials: PS
authors.lastname: Wu
authors.forename: Chiang-Hung
authors.initials: CH
authors.lastname: Chou
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Yan
authors.forename: Hsuan
authors.initials: H
authors.lastname: Liu
authors.forename: Shih-Yen
authors.initials: SY
authors.lastname: Weng
authors.forename: Hsin-Fang
authors.initials: HF
authors.lastname: Yang-Yen
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000172:deficiency* / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D016213:Cyclins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000002:abnormalities; D005260:Female; D005313:Fetal Death; D005347:Fibroblasts / Q000166:cytology; D016193:G1 Phase; D016195:G2 Phase; D005775:Gastrula / Q000378:metabolism; D018390:Gene Targeting; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D009154:Mutation / Q000235:genetics; D009928:Organ Specificity; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D016213:Cyclins; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1