Exploring the importance of predicted camel NRAP exon 4 for environmental adaptation using a mouse model

使用小鼠模型探索预测的骆驼 NRAP 外显子 4 对环境适应的重要性

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作者:Sung-Yeon Lee, Bo-Young Lee, Byeonghwi Lim, Rasel Uzzaman, Goo Jang, Kwan-Suk Kim

Abstract

Camels possess exceptional adaptability, allowing them to withstand extreme temperatures in desert environments. They conserve water by reducing their metabolic rate and regulating body temperature. The heart of the camel plays a crucial role in this adaptation, with specific genes expressed in cardiac tissue that are essential for mammalian adaptation, regulating cardiac function and responding to environmental stressors. One such gene, nebulin-related-anchoring protein (NRAP), is involved in the assembly of myofibrils and the transmission of force within the heart. In our study of the NRAP gene across various livestock species, including three camel species, we identified a camel-specific exon region in the NRAP transcripts. This additional exon (exon 4) contains an open reading frame predicted in camels. To investigate its function, we generated knock-in mice expressing camel NRAP exon 4. These 'camelized mice' exhibited normal phenotypic characteristics compared with wild-type mice but showed elevated body temperatures under cold stress. Transcriptome analyses of the hearts from camelized mice under cold stress revealed differentially expressed inflammatory cytokine genes, known to influence cardiac function by modulating the contractility of cardiac muscle cells. We propose further investigations utilizing these camelized mice to explore these findings in greater depth.

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