title: Two Zebrafish hsd3b Genes Are Distinct in Function, Expression, and Evolution.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jen-Chieh
authors.initials: JC
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Shing
authors.initials: S
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Pei-Hung
authors.initials: PH
authors.lastname: Ho
authors.affiliation: 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.
authors.forename: Hwei-Jan
authors.initials: HJ
authors.lastname: Hsu
authors.affiliation: 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.
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.affiliation: 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.
authors.forename: Bon-chu
authors.initials: BC
authors.lastname: Chung
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019556:COS Cells; D002522:Chlorocebus aethiops; D004625:Embryo, Nonmammalian; D019143:Evolution, Molecular; D015971:Gene Expression Regulation, Enzymologic; D055785:Gene Knockdown Techniques; D009097:Multienzyme Complexes / Q000235:genetics* / Q000502:physiology; D010802:Phylogeny; D011375:Progesterone Reductase / Q000235:genetics* / Q000502:physiology; D013251:Steroid Isomerases / Q000235:genetics* / Q000502:physiology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; C533068:3 beta-hydroxysteroid dehydrogenase type II; D011375:Progesterone Reductase; D013251:Steroid Isomerases