Global Deletion of TSPO Does Not Affect the Viability and Gene Expression Profile.

Translocator Protein (18kDa, TSPO) is a mitochondria outer membrane transmembrane protein and which expression is elevated during inflammation and injury. However, the exact function of TSPO is still controversial. Here, we constructed TSPO global knockout (KO) mice by Cre-LoxP system independently, which abolished TSPO protein expression in all tissues and shown normal phenotypes. The birth rate of TSPO heterozygote (Het)/Het breeding was consistent with the Mendel's Law, suggesting a normal viability of TSPO KO mice at birth. RNAseq analysis showed no significant difference in the gene expression profile of lung tissues from TSPO KO mice compared with that of wild type mice, even the genes associated with bronchial alveoli immune homeostasis. The alveolar macrophage population was also not affected by TSPO deletion in the physiological condition. Our findings contradicts the results of Papadopoulos, but confirmed Selvaraj's findings. This study reveals TSPO deficiency does not affect the viability and bronchial alveoli immune homeostasis. Lung tissue mRNA profiles of wild type (WT) and TSPO knockout (KO) mice were generated by deep sequencing using Illumina's digital gene expression tag profiling (DGE) system, in triplicate. Every lung tissue RNA samples [WT (D,H,Z) and KO (B,F,M)] were pooled from three tissue samples of littermates.18kDa转位蛋白（Translocator Protein, TSPO）是定位于线粒体外膜的跨膜蛋白，其表达水平在炎症与损伤状态下会升高。然而，TSPO的确切功能至今仍存在争议。本研究独立借助Cre-LoxP重组酶系统构建了TSPO全身敲除（KO）小鼠模型，该模型可在所有组织中完全敲除TSPO蛋白的表达，且小鼠表型无异常。TSPO杂合子（Het）与杂合子繁育的子代出生率符合孟德尔遗传定律，提示TSPO敲除小鼠在出生时的存活率处于正常水平。RNA测序（RNAseq）分析结果显示，与野生型小鼠相比，TSPO敲除小鼠的肺组织基因表达谱无显著差异，即便针对与支气管肺泡免疫稳态相关的基因亦是如此。生理状态下，肺泡巨噬细胞群体同样未受到TSPO敲除的影响。本研究结论与Papadopoulos等人的研究结果相悖，但验证了Selvaraj等人的发现。本研究揭示，TSPO缺失并不会对小鼠的存活率以及支气管肺泡免疫稳态造成影响。本研究采用Illumina数字基因表达标签谱（DGE）系统的深度测序技术，对野生型（WT）与TSPO敲除（KO）小鼠的肺组织mRNA进行了测序，每组设置3次生物学重复。所有肺组织RNA样本[野生型组（D、H、Z）与敲除组（B、F、M）]均取自同窝3只小鼠的肺组织混合样本。