The Caenorhabditis elegans ortholog of C21orf80, a potential new protein O-fucosyltransferase, is required for normal development

Autor: Fritz Mueller, Krisztina Takács-Vellai, Tibor Vellai, Alexandre Reymond, Olivier Menzel, Stylianos E. Antonarakis, Michel Guipponi
Rok vydání: 2004
Předmět:
Embryo
Nonmammalian
Chromosomes
Human
Pair 21
Transgene
Molecular Sequence Data
ved/biology.organism_classification_rank.species
Transfection
Fucosyltransferases/chemistry/ genetics/ metabolism
Cell Line
Open Reading Frames/genetics
Open Reading Frames
RNA interference
Morphogenesis
Genetics
Animals
Humans
Amino Acid Sequence
Cloning
Molecular
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Model organism
Gene
Conserved Sequence
ddc:616
biology
ved/biology
Conserved Sequence/ genetics
Gene Expression Profiling
Chromosomes
Human
Pair 21/genetics
Gene Expression Regulation
Developmental
Fucosyltransferases
biology.organism_classification
Phenotype
Gene expression profiling
Caenorhabditis elegans/ embryology/enzymology/ genetics/metabolism
Fertility
Caenorhabditis elegans Proteins/chemistry/ genetics/ metabolism
Fertility/genetics
RNA Interference
Chromosome 21
Embryo
Nonmammalian/abnormalities/metabolism
Zdroj: Genomics, Vol. 84, No 2 (2004) pp. 320-330
ISSN: 0888-7543
DOI: 10.1016/j.ygeno.2004.04.002
Popis: 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.
Databáze: OpenAIRE
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