title: Knockdown of bicaudal C in zebrafish (Danio rerio) causes cystic kidneys: a nonmammalian model of polycystic kidney disease.
abstract: Polycystic kidney disease (PKD) is one of the leading causes of end-stage renal disease in humans and is characterized by progressive cyst formation, renal enlargement, and abnormal tubular development. Currently, there is no cure for PKD. Although a number of PKD genes have been identified, their precise role in cystogenesis remains unclear. In the jcpk mouse model of PKD, mutations in the bicaudal C gene (Bicc1) are responsible for the cystic phenotype; however, the function of Bicc1 is unknown. In this study, we establish an alternative, nonmammalian zebrafish model to study the role of Bicc1 in PKD pathogenesis. Antisense morpholinos were used to evaluate loss of Bicc1 function in zebrafish. The resulting morphants were examined histologically for kidney cysts and structural abnormalities. Immunostaining and fluorescent dye injection were used to evaluate pronephric cilia and kidney morphogenesis. Knockdown of zebrafish Bicc1 expression resulted in the formation of kidney cysts; however, defects in kidney structure or pronephric cilia were not observed. Importantly, expression of mouse Bicc1 rescues the cystic phenotype of the morphants. These results demonstrate that the function of Bicc1 in the kidney is evolutionarily conserved, thus supporting the use of zebrafish as an alternative in vivo model to study the role of mammalian Bicc1 in renal cyst formation.
authors.affiliation: Genetics Area Program and Department of Veterinary Pathobiology, Research Animal Diagnostic Laboratory, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
authors.forename: Denise J
authors.initials: DJ
authors.lastname: Bouvrette
authors.forename: Vinoth
authors.initials: V
authors.lastname: Sittaramane
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Heidel
authors.forename: Anand
authors.initials: A
authors.lastname: Chandrasekhar
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Bryda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016376:Oligonucleotides, Antisense; D016601:RNA-Binding Proteins; D029961:Zebrafish Proteins; C551039:bicc1b protein, zebrafish