title: Developmental roles of D-bifunctional protein-A zebrafish model of peroxisome dysfunction.
abstract: The peroxisome is an intracellular organelle that responds dynamically to environmental changes. Various model organisms have been used to study the roles of peroxisomal proteins in maintaining cellular homeostasis. By taking advantage of the zebrafish model whose early stage of embryogenesis is dependent on yolk components, we examined the developmental roles of the D-bifunctional protein (Dbp), an essential enzyme in the peroxisomal β-oxidation. The knockdown of dbp in zebrafish phenocopied clinical manifestations of its deficiency in human, including defective craniofacial morphogenesis, growth retardation, and abnormal neuronal development. Overexpression of murine Dbp rescued the morphological phenotypes induced by dbp knockdown, indicative of conserved roles of Dbp during zebrafish and mammalian development. Knockdown of dbp impaired normal development of blood, blood vessels, and most strikingly, endoderm-derived organs including the liver and pancreas - a phenotype not reported elsewhere in connection with peroxisome dysfunction. Taken together, our results demonstrate for the first time that zebrafish might be a useful model animal to study the role of peroxisomes during vertebrate development.
authors.affiliation: Center for Metabolic Function Regulation, and Department of Microbiology, School of Medicine, Wonkwang University, Iksan 570-749, Korea.
authors.forename: Yong-Il
authors.initials: YI
authors.lastname: Kim
authors.forename: Sushil
authors.initials: S
authors.lastname: Bhandari
authors.forename: Joon No
authors.initials: JN
authors.lastname: Lee
authors.forename: Kyeong-Won
authors.initials: KW
authors.lastname: Yoo
authors.forename: Se-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Gi-Su
authors.initials: GS
authors.lastname: Oh
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Meyoung
authors.initials: M
authors.lastname: Cho
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Kwak
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Choe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004195:Disease Models, Animal; D047108:Embryonic Development; D041981:Gastrointestinal Tract / Q000002:abnormalities; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D055495:Neurogenesis; D018901:Peroxisomal Disorders / Q000201:enzymology* / Q000235:genetics; D064029:Peroxisomal Multifunctional Protein-2 / Q000235:genetics* / Q000378:metabolism; D020675:Peroxisomes / Q000201:enzymology; D015017:Yolk Sac / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; D064029:Peroxisomal Multifunctional Protein-2