Developmental roles of D-bifunctional protein-A zebrafish model of peroxisome dysfunction

• Published in: Molecules and cells 2014, 37(1), , pp.74-80
• Main Authors: Kim, Yong-Il, Bhandari, Sushil, Lee, Joon No, Yoo, Kyeong-Won, Kim, Se-Jin, Oh, Gi-Su, Kim, Hyung-Jin, Cho, Meyoung, Kwak, Jong-Young, So, Hong-Seob, Park, Raekil, Choe, Seong-Kyu
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Conserved Sequence; Disease Models, Animal; Embryonic Development; Gastrointestinal Tract - abnormalities; Gene Expression; Gene Knockdown Techniques; Genetic Complementation Test; Humans; Mice; Molecular Sequence Data; Neurogenesis; Peroxisomal Disorders - enzymology; Peroxisomal Disorders - genetics; Peroxisomal Multifunctional Protein-2 - genetics; Peroxisomal Multifunctional Protein-2 - metabolism; Peroxisomes - enzymology; Yolk Sac - metabolism; Zebrafish - embryology; Zebrafish - genetics; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; 생물학
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2014.2300

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.