Department of Stem Cell and Regenerative Biotechnology, Humanized Pig Research Centre (SRC), Konkuk University, Seoul 143-701, Korea.
Molecules. 2018 Feb 27;23(3):527. doi: 10.3390/molecules23030527.
The knockout (KO) mouse is a well-established immune-compromised animal model for biomedical research. A comparative study identified the deregulated expression of microRNAs (miRNAs) and messenger RNAs (mRNAs) in KO mice. However, the interaction between deregulated genes and miRNAs in the alteration of systemic (cardiac, renal, hepatic, nervous, and hematopoietic) regulations and the synthesis of biomolecules (such as l-tryptophan, serotonin, melatonin, dopamine, alcohol, noradrenaline, putrescine, and acetate) are unclear. In this study, we analyzed both miRNA and mRNA expression microarray data from KO and wild type mice to investigate the possible role of miRNAs in systemic regulation and biomolecule synthesis. A notable finding obtained from this analysis is that the upregulation of several genes which are target molecules of the downregulated miRNAs in KO mice, can potentially trigger the degradation of l-tryptophan, thereby leading to the systemic impairment and alteration of biomolecules synthesis as well as changes in behavioral patterns (such as stress and fear responses, and social recognition memory) in gene-depleted mice. These findings were either not observed or not explicitly described in other published KO transcriptome analyses. In conclusion, we have provided an indication of miRNA-dependent regulations of clinical and pathological conditions in cardiac, renal, hepatic, nervous, and hematopoietic systems in KO mice. These results may significantly contribute to the prediction of clinical disease caused by deficiency.
敲除（KO）小鼠是一种成熟的免疫缺陷动物模型，常用于生物医学研究。一项比较研究确定了 KO 小鼠中 microRNAs（miRNAs）和信使 RNAs（mRNAs）的失调表达。然而，在系统性（心脏、肾脏、肝脏、神经和造血）调节和生物分子（如 l-色氨酸、血清素、褪黑素、多巴胺、酒精、去甲肾上腺素、腐胺和乙酸盐）合成的改变中，失调基因和 miRNAs 之间的相互作用尚不清楚。在这项研究中，我们分析了 KO 和野生型小鼠的 miRNA 和 mRNA 表达微阵列数据，以研究 miRNAs 在系统性调节和生物分子合成中的可能作用。从该分析中得到的一个显著发现是，KO 小鼠中下调 miRNAs 的靶分子的几个基因的上调，可能会触发 l-色氨酸的降解，从而导致全身受损和生物分子合成改变，以及行为模式（如应激和恐惧反应以及社会识别记忆）的变化）在基因耗竭的小鼠中。这些发现或未在其他已发表的 KO 转录组分析中观察到，或未明确描述。总之，我们提供了 KO 小鼠心脏、肾脏、肝脏、神经和造血系统中临床和病理状况依赖于 miRNA 调节的迹象。这些结果可能对预测由 KO 引起的临床疾病有重要意义。
