title: ACE2 orthologues in non-mammalian vertebrates (Danio, Gallus, Fugu, Tetraodon and Xenopus).
abstract: Angiotensin-converting enzyme 2 (ACE2), a newly identified member in the renin-angiotensin system (RAS), acts as a negative regulator of ACE. It is mainly expressed in cardiac blood vessels and the tubular epithelia of kidneys and abnormal expression has been implicated in diabetes, hypertension and heart failure. The mechanism and physiological function of this zinc metallopeptidase in mammals are not yet fully understood. Non-mammalian vertebrate models offer attractive and simple alternatives that could facilitate the exploration of ACE2 function. In this paper we report the in silico analysis of Ace2 genes from the Gallus (chicken), Xenopus (frog), Fugu and Tetraodon (pufferfish) genome assembly databases, and from the Danio (zebrafish) cDNA library. Exon ambiguities of Danio and Xenopus Ace2s were resolved by RT-PCR and 3'RACE. Analyses of the exon-intron structures, alignment, phylogeny and hydrophilicity plots, together with the conserved synteny among these vertebrates, support the orthologous relationship between mammalian and non-mammalian ACE2s. The putative promoters of Ace2 from human, Tetraodon and Xenopus tropicalis drove the expression of enhanced green fluorescent protein (EGFP) specifically in the heart tissue of transgenic Xenopus thus making it a suitable model for future functional genomic studies. Additionally, the search for conserved cis-elements resulted in the discovery of WGATAR motifs in all the putative Ace2 promoters from 7 different animals, suggesting a possible role of GATA family transcriptional factors in regulating the expression of Ace2.
authors.affiliation: Institute of Molecular and Cell Biology, Proteos, Singapore. mcbccf@imcb.a-star.edu.sg
authors.forename: Chih-Fong
authors.initials: CF
authors.lastname: Chou
authors.forename: Chay Boon
authors.initials: CB
authors.lastname: Loh
authors.forename: Yik Khoon
authors.initials: YK
authors.lastname: Foo
authors.forename: Shuo
authors.initials: S
authors.lastname: Shen
authors.forename: Burtram C
authors.initials: BC
authors.lastname: Fielding
authors.forename: Timothy H P
authors.initials: TH
authors.lastname: Tan
authors.forename: Sehaam
authors.initials: S
authors.lastname: Khan
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.forename: Yee-Joo
authors.initials: YJ
authors.lastname: Tan
authors.forename: Jianlin
authors.initials: J
authors.lastname: Fu
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002645:Chickens / Q000235:genetics; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics; D023741:Takifugu / Q000235:genetics; D023721:Tetraodontiformes / Q000235:genetics; D014714:Vertebrates / Q000235:genetics*; D014981:Xenopus / Q000235:genetics; D015027:Zebrafish / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2