Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-01-01 Epub Date: 2023-11-13 DOI:10.1152/physiolgenomics.00084.2023
Jan Šilhavý, Petr Mlejnek, Miroslava Šimáková, František Liška, Hana Malínská, Irena Marková, Martina Hüttl, Denisa Miklánková, Dita Mušálková, Viktor Stránecký, Stanislav Kmoch, Eva Sticová, Marek Vrbacký, Tomáš Mráček, Michal Pravenec
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Abstract

Recently, we have identified a recessive mutation, an abnormal coat appearance in the BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the spontaneously hypertensive rat (SHR) and Brown Norway rat (BN-Lx) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the tuftelin 1 (Tuft1) gene on chromosome 2, which resulted in a premature stop codon. Compared with wild-type BXH6 rats, BXH6-Tuft1 mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart. Reduced adiposity was associated with decreased serum glucose and insulin and increased insulin-stimulated glycogenesis in skeletal muscle. In addition, mutant rats had lower serum monocyte chemoattractant protein-1 and leptin levels, indicative of reduced inflammation. Analysis of the liver proteome identified differentially expressed proteins from fatty acid metabolism and β-oxidation, peroxisomes, carbohydrate metabolism, inflammation, and proteasome pathways. These results provide evidence for the important role of the Tuft1 gene in the regulation of lipid and glucose metabolism and suggest underlying molecular mechanisms.NEW & NOTEWORTHY A new spontaneous mutation, abnormal hair appearance in the rat, has been identified as a nonfunctional tuftelin 1 (Tuft1) gene. The pleiotropic effects of this mutation regulate glucose and lipid metabolism. Analysis of the liver proteome revealed possible molecular mechanisms for the metabolic effects of the Tuft1 gene.

Tuft1 (tuftelin 1)基因自发无义突变与大鼠毛发外观异常和糖脂代谢改善有关。
最近,我们在重组自交系(RI) HXB/BXH的成员BXH6菌株中发现了一个隐性突变,即外壳外观异常。RI系来源于SHR(自发性高血压大鼠)和BN-Lx(褐挪威大鼠)祖细胞。对突变大鼠进行全基因组测序,发现2号染色体上Tuft1 (tuftelin 1)基因发生195875980 G/A突变,导致一个过早终止密码子。与野生型BXH6大鼠相比,BXH6- tuft1突变大鼠由于内脏脂肪减少和肝脏和心脏的异位脂肪堆积而表现出较低的体重。肥胖的减少与血清葡萄糖和胰岛素的降低以及胰岛素刺激的骨骼肌糖生成的增加有关。此外,突变大鼠血清MCP-1和瘦素水平较低,表明炎症减轻。肝脏蛋白质组分析鉴定了脂肪酸代谢和β氧化、过氧化物酶体、碳水化合物代谢、炎症和蛋白酶体途径中差异表达的蛋白质。这些结果为Tuft1基因在脂质和糖代谢调控中的重要作用提供了证据,并提出了潜在的分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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