PUBLICATION

Zebrafish mutations affecting cilia motility share similar cystic phenotypes and suggest a mechanism of cyst formation that differs from pkd2 morphants

Authors
Sullivan-Brown, J., Schottenfeld, J., Okabe, N., Hostetter, C.L., Serluca, F.C., Thiberge, S.Y., and Burdine, R.D.
ID
ZDB-PUB-080124-12
Date
2008
Source
Developmental Biology   314(2): 261-275 (Journal)
Registered Authors
Burdine, Rebecca, Hostetter, Christine, Okabe, Noriko, Schottenfeld, Jodi, Serluca, Fabrizio, Sullivan-Brown, Jessica
Keywords
Pronephros, Cyst, Kidney, Zebrafish, Cilia, locke, switch hitter, lrrc50, kurly, pkd2, oda7, Nephron
MeSH Terms
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Mutagenesis
  • Animals
  • Microscopy, Video
  • Mutation*
  • Kidney Tubules/physiology
  • Kidney Glomerulus/physiology
  • Cloning, Molecular
  • Zebrafish Proteins/genetics*
  • Cilia/physiology*
  • Phenotype
  • Nephrons/embryology
  • Nephrons/physiology
  • Nephrons/physiopathology
  • Embryo, Nonmammalian/physiology
(all 16)
PubMed
18178183 Full text @ Dev. Biol.
Abstract
Zebrafish are an attractive model for studying the earliest cellular defects occurring during renal cyst formation because its kidney (the pronephros) is simple and genes that cause cystic kidney diseases (CKD) in humans, cause pronephric dilations in zebrafish. By comparing phenotypes in three different mutants, locke, swt and kurly, we find that dilations occur prior to 48 hpf in the medial tubules, a location similar to where cysts form in some mammalian diseases. We demonstrate that the first observable phenotypes associated with dilation include cilia motility and luminal remodeling defects. Importantly, we show that some phenotypes common to human CKD, such as an increased number of cells, are secondary consequences of dilation. Despite having differences in cilia motility, locke, swt and kurly share similar cystic phenotypes, suggesting that they function in a common pathway. To begin to understand the molecular mechanisms involved in cyst formation, we have cloned the swt mutation and find that it encodes a novel leucine rich repeat containing protein (LRRC50), which is thought to function in correct dynein assembly in cilia. Finally, we show that knock-down of polycystic kidney disease 2 (pkd2) specifically causes glomerular cysts and does not affect cilia motility, suggesting multiple mechanisms exist for cyst formation.
Genes / Markers
Figures
Figure Gallery (7 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fk03a
    Point Mutation
    tm304
      Point Mutation
      tm317b
        Point Mutation
        to237b
          Point Mutation
          1 - 4 of 4
          Show
          Human Disease / Model
          1 - 1 of 1
          Show
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          pkd2MO3-pkd2MRPHLNO
          1 - 1 of 1
          Show
          Fish
          Antibodies
          Orthology
          No data available
          Engineered Foreign Genes
          No data available
          Mapping
          Entity Type Entity Symbol Location
          Featurefk03aChr: 7 Details
          SSLPz11119Chr: 7 Details
          SSLPz15270Chr: 7 Details
          1 - 3 of 3
          Show