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单羧酸转运蛋白SLC16A6调节斑马鱼的成年体长并与人类身高相关。

The Monocarboxylate Transporter SLC16A6 Regulates Adult Length in Zebrafish and Is Associated With Height in Humans.

作者信息

Karanth Santhosh, Schlegel Amnon

机构信息

University of Utah Molecular Medicine Program, University of Utah School of Medicine, Salt Lake City, UT, United States.

Division of Endocrinology, Metabolism & Diabetes, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, United States.

出版信息

Front Physiol. 2019 Jan 14;9:1936. doi: 10.3389/fphys.2018.01936. eCollection 2018.

Abstract

When fasted as larvae or fed ketogenic diets as adults, homozygous zebrafish mutants develop hepatic steatosis because their livers cannot export the major ketone body β-hydroxybutyrate, diverting liver-trapped ketogenic carbon atoms to triacylglycerol. Here, we find that mutants are longer than their wild-type siblings. This effect is largely not sexually dimorphic, nor is it affected by dietary fat content on a pure genetic background. A mixed genetic background alters the proportionality of mass to length modestly. We also observe that non-coding variations in the 5'-untranslated region and first intron, and coding variations within the fifth exon of the orthologous human gene locus are highly significantly associated with human height. Since both zebrafish and human orthologs of SLC16A6 are expressed in multiple locations, this gene likely regulates height through modulating transport of monocarboxylic acids in several tissues.

摘要

当幼虫期禁食或成年期喂食生酮饮食时,纯合子斑马鱼突变体出现肝脂肪变性,因为它们的肝脏无法输出主要酮体β-羟基丁酸酯,从而将肝脏中捕获的生酮碳原子转移到三酰甘油中。在这里,我们发现突变体比它们的野生型同胞更长。这种效应在很大程度上没有性别差异,在纯遗传背景下也不受饮食脂肪含量的影响。混合遗传背景会适度改变质量与长度的比例。我们还观察到,直系同源人类基因座的5'非翻译区和第一内含子中的非编码变异,以及第五外显子内的编码变异与人类身高高度显著相关。由于SLC16A6的斑马鱼和人类直系同源物都在多个位置表达,该基因可能通过调节几种组织中一元羧酸的转运来调节身高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3686/6339906/276d4c0ee534/fphys-09-01936-g001.jpg

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