Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, P.R. China.
Int J Mol Med. 2018 Jan;41(1):381-390. doi: 10.3892/ijmm.2017.3196. Epub 2017 Oct 19.
Coiled-coil domain containing 134 (CCDC134), a characterized secreted protein, may serve as an immune cytokine and illustrates its potent antitumor effects by augmenting CD8+ T-cell-mediated immunity. Additionally, CCDC134 may also act as a novel regulator of human alteration/deficiency in activation 2a, and be involved in the p300-CBP-associated factor complex and affect its acetyltransferase activity. To clarify the biological and pathological function of CCDC134, the present study generated a viable and fertile Ccdc134fl/fl mouse strain that allowed temporal and spatial control of gene ablation. Ccdc134-/- embryos generated by crossing of Ccdc134fl/fl mice with human β-actin-Cre or zona pellucida 3-Cre transgenic mice were embryonic lethal from embryonic day (E)12.5 to birth. Ccdc134 loss was associated with severe hemorrhages in the brain ventricular space and neural tube, pale and abnormal livers, cardiac hypertrophy and placental distress. Furthermore, it was demonstrated that a fraction of E13.5 fetal livers and brains exhibited reduced cell proliferation and vascular endothelial cell defects. CCDC134 also exhibited a dynamic and specific expression pattern during embryo development. The present results suggest that Ccdc134 may have specific biological functions in regulating mouse embryonic development.
卷曲螺旋结构域蛋白 134（CCDC134）是一种已鉴定的分泌蛋白，可作为免疫细胞因子，通过增强 CD8+T 细胞介导的免疫来发挥其强大的抗肿瘤作用。此外，CCDC134 还可以作为人类激活 2a 缺陷/改变的新型调节剂，参与 p300-CBP 相关因子复合物，并影响其乙酰转移酶活性。为了阐明 CCDC134 的生物学和病理学功能，本研究构建了一种具有活力和生育能力的 Ccdc134fl/fl 小鼠品系，允许对基因缺失进行时空控制。通过将 Ccdc134fl/fl 小鼠与人类β-肌动蛋白-Cre 或透明带 3-Cre 转基因小鼠杂交产生的 Ccdc134-/- 胚胎从胚胎第 12.5 天到出生时致死。Ccdc134 缺失与脑室内严重出血和神经管、苍白和异常肝脏、心脏肥大和胎盘窘迫有关。此外，还表明一部分 E13.5 胎肝和胎脑表现出细胞增殖减少和血管内皮细胞缺陷。CCDC134 在胚胎发育过程中也表现出动态和特异性的表达模式。本研究结果表明，Ccdc134 可能在调节小鼠胚胎发育中具有特定的生物学功能。
