title: The Caenorhabditis elegans ortholog of C21orf80, a potential new protein O-fucosyltransferase, is required for normal development.
abstract: Down syndrome (DS), as a phenotypic result of trisomy 21, is the most frequent aneuploidy at birth and the most common known genetic cause of mental retardation. DS is also characterized by other phenotypes affecting many organs, including brain, muscle, heart, limbs, gastrointestinal tract, skeleton, and blood. Any of the human chromosome 21 (Hsa21) genes may contribute to some of the DS phenotypes. To determine which of the Hsa21 genes are involved in DS, the effects of disrupting and overexpressing individual human gene orthologs in model organisms, such as the nematode Caenorhabditis elegans, can be analyzed. Here, we isolated and characterized C21orf80 (human chromosome 21 open reading frame 80), a potential novel protein O-fucosyltransferase gene that encodes three alternatively spliced transcripts. Transient expression of tagged C21orf80 proteins suggests a primary intracellular localization in the Golgi apparatus. To gain insight into the biological role of C21orf80 and its potential role in DS, we isolated its C. elegans ortholog, pad-2, and performed RNA interference (RNAi) and overexpression experiments. pad-2(RNAi) embryos showed failure to undergo normal morphogenesis. Transgenic worms with elevated dosage of pad-2 displayed severe body malformations and abnormal neuronal development. These results show that pad-2 is required for normal development and suggest potential roles for C21orf80 in the pathogenesis of DS.
authors.affiliation: Division of Medical Genetics, University of Geneva Medical School, 1 Rue Michel Servet, 1211 Geneva 4, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Menzel
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
authors.forename: Krisztina
authors.initials: K
authors.lastname: Takacs-Vellai
authors.forename: Alexandre
authors.initials: A
authors.lastname: Reymond
authors.forename: Fritz
authors.initials: F
authors.lastname: Mueller
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Michel
authors.initials: M
authors.lastname: Guipponi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000378:metabolism; D005298:Fertility / Q000235:genetics; D005647:Fucosyltransferases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016366:Open Reading Frames / Q000235:genetics; D034622:RNA Interference; D014162:Transfection
chemical_list: D029742:Caenorhabditis elegans Proteins; D005647:Fucosyltransferases; C495598:Pad-2 protein, C elegans; C495567:POFUT2 protein, human