Lin Jen-Chieh, Hu Shing, Ho Pei-Hung, Hsu Hwei-Jan, Postlethwait John H, Chung Bon-chu
Institute of Genome Sciences (J.-C.L., P.-H.H., B.-c.C.), National Yang-Ming University, Taipei, 112 Taiwan; Institute of Molecular Biology (J.-C.L., S.H., P.-H.H., H.-J.H., B.-c.C.), Academia Sinica, Taipei, 115 Taiwan; and Institute of Neuroscience (J.H.P.), University of Oregon, Eugene, Oregon 97403.
Endocrinology. 2015 Aug;156(8):2854-62. doi: 10.1210/en.2014-1584. Epub 2015 May 14.
HSD3B catalyzes the synthesis of δ4 steroids such as progesterone in the adrenals and gonads. Individuals lacking HSD3B2 activity experience congenital adrenal hyperplasia with imbalanced steroid synthesis. To develop a zebrafish model of HSD3B deficiency, we characterized 2 zebrafish hsd3b genes. Our phylogenetic and conserved synteny analyses showed that the tandemly duplicated human HSD3B1 and HSD3B2 genes are coorthologs of zebrafish hsd3b1 on chromosome 9 (Dre9), whereas the gene called hsd3b2 resides on Dre20 in an ancestral chromosome segment, from which its ortholog was lost in the tetrapod lineage. Zebrafish hsd3b1(Dre 9) was expressed in adult gonads and headkidney, which contains interrenal glands, the zebrafish counterpart of the tetrapod adrenal. Knockdown of hsd3b1(Dre 9) caused the interrenal and anterior pituitary to expand and pigmentation to increase, resembling human HSD3B2 deficiency. The zebrafish hsd3b2(Dre 20) gene was expressed in zebrafish early embryos as maternal transcripts that disappeared 1 day after fertilization. Morpholino inactivation of hsd3b2(Dre 20) led to embryo elongation, which was rescued by the injection of hsd3b2 mRNA. Thus, zebrafish hsd3b2(Dre 20) evolved independently of hsd3b1(Dre 9) with a morphogenetic function during early embryogenesis. Zebrafish hsd3b1(Dre 9), on the contrary, functions like mammalian HSD3B2, whose deficiency leads to congenital adrenal hyperplasia.
HSD3B催化肾上腺和性腺中δ4类固醇（如孕酮）的合成。缺乏HSD3B2活性的个体患有先天性肾上腺增生，类固醇合成失衡。为了建立HSD3B缺乏的斑马鱼模型，我们对2个斑马鱼hsd3b基因进行了表征。我们的系统发育和保守同线性分析表明，串联重复的人类HSD3B1和HSD3B2基因是9号染色体（Dre9）上斑马鱼hsd3b1的共直系同源基因，而名为hsd3b2的基因位于Dre20上的一个祖先染色体片段中，其直系同源基因在四足动物谱系中丢失。斑马鱼hsd3b1（Dre 9）在成年性腺和头肾中表达，头肾包含间肾腺，即四足动物肾上腺的斑马鱼对应物。敲低hsd3b1（Dre 9）会导致间肾和垂体前叶扩张以及色素沉着增加，类似于人类HSD3B2缺乏症。斑马鱼hsd3b2（Dre 20）基因在斑马鱼早期胚胎中作为母源转录本表达，在受精后1天消失。对hsd3b2（Dre 20）进行吗啉代失活会导致胚胎伸长，注射hsd3b2 mRNA可挽救这种情况。因此，斑马鱼hsd3b2（Dre 20）在早期胚胎发育过程中独立于hsd3b1（Dre 9）进化，具有形态发生功能。相反，斑马鱼hsd3b1（Dre 9）的功能类似于哺乳动物的HSD3B2，其缺乏会导致先天性肾上腺增生。
