RRC ID 31775
著者 Hashimoto H, Miyamoto R, Watanabe N, Shiba D, Ozato K, Inoue C, Kubo Y, Koga A, Jindo T, Narita T, Naruse K, Ohishi K, Nogata K, Shin-I T, Asakawa S, Shimizu N, Miyamoto T, Mochizuki T, Yokoyama T, Hori H, Takeda H, Kohara Y, Wakamatsu Y.
タイトル Polycystic kidney disease in the medaka (Oryzias latipes) pc mutant caused by a mutation in the Gli-Similar3 (glis3) gene.
ジャーナル PLoS One
Abstract Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients.
巻・号 4(7)
ページ e6299
公開日 2009-7-17
DOI 10.1371/journal.pone.0006299
PMID 19609364
PMC PMC2706989
MeSH Animals Base Sequence Cell Proliferation DNA Primers Fluorescent Dyes Gene Knockdown Techniques In Situ Hybridization Mutation* Oryzias Pancreas / metabolism Polycystic Kidney Diseases / genetics* Polycystic Kidney Diseases / pathology Subcellular Fractions / metabolism Transcription Factors / genetics* Zinc Fingers*
IF 2.74
引用数 20
WOS 分野 DEVELOPMENTAL BIOLOGY
リソース情報
メダカ pc (MT83) HNI-II (IB176)