MicroRNA and Transcriptomic Profiling Showed miRNA-Dependent Impairment of Systemic Regulation and Synthesis of Biomolecules in Rag2 KO Mice.

Yun-Jung Choi,Abu Reza,Jin-Hoi Kim

doi:10.3390/molecules23030527

Yun-Jung Choi, Abu Reza + Show 1 more

Open Access

https://doi.org/10.3390/molecules23030527

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Journal: Molecules (Basel, Switzerland)	Publication Date: Feb 27, 2018
Citations: 2	License type: CC BY 4.0

Affiliation: Konkuk University

Abstract

The Rag2 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 Rag2 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 Rag2 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 Rag2 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 Rag2 gene-depleted mice. These findings were either not observed or not explicitly described in other published Rag2 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 Rag2 KO mice. These results may significantly contribute to the prediction of clinical disease caused by Rag2 deficiency.

Highlights

The Rag2 knockout (KO) mouse is one of the most important immune-compromised animal models used in preclinical studies and biomedical research [1]
Studies have shown that the Rag2 KO mice show alteration in stress and fear responses when compared with immune competent mice [4], and the T cells play important roles during these stress and fear responses by contributing to the learning and memory processes [4]
We analyzed the data obtained from a recent comparative miRNA and messenger RNAs (mRNAs) microarrays in Rag2 KO versus wild type (WT) mice [1], and focused on the miRNAs that mediated systemic regulation and biomolecule metabolism in Rag2 KO mice compared to the WT counterparts

Summary

Introduction

The Rag knockout (KO) mouse is one of the most important immune-compromised animal models used in preclinical studies and biomedical research [1]. Rag KO mice have an impaired V(D)J recombination status. The V(D)J recombination processes are regulated by a complex of Rag and. Rag proteins, which can create DNA double-strand breaks at conserved recombination signal sequences, contributing to the development of both B- and T-lymphocytes [1]. Studies have shown that the Rag KO mice show alteration in stress and fear responses when compared with immune competent mice [4], and the T cells play important roles during these stress and fear responses by contributing to the learning and memory processes [4].

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