Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant

Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes) pc mutant.BackgroundPolycystic kidney disease (PKD) is a common hereditary disease. A number of murine and zebrafish mutants have been generated and used for the study of PKD as metanephric and pronephric models, respectively. Here, we report a medaka (Oryzias latipes) mutant that develops numerous cysts in the kidney in adulthood fish in an autosomal-recessive manner as a mesonephric model of PKD.MethodsThe phenotypes of the medaka pc mutant were described in terms of morphologic, histologic, and ultrastructural features. The pc see-through stock was produced by crossing a pc mutant and a fish from the see-through stock and used for observing the kidney through the transparent body wall of a live fish.ResultsThe mutant developed bilateral massive enlargement of the kidney in adulthood. They sexually matured normally within 2 months of age and died within 6 months of age. The affected kidney was occupied by numerous, fluid-filled cysts, which were lined by attenuated squamous epithelial cells. Developmentally, cystic formation began in the pronephros in 10-day-old fry and in the mesonephros in 20-day-old fry at the microscopic level. The pc see-through stock was useful in observing disease progression in live fish.ConclusionThe kidney disorder that develops in the medaka pc mutant is a mesonephric counterpart of PKD, particularly an autosomal-dominant PKD, based on its morphologic, histologic, and ultrastructural features, and slow progression

Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

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

ニワトリ初期胚の原条と脊索における細胞周期

京都大学0048新制・課程博士理学博士理博第140号新制||理||97(附属図書館)2264京都大学大学院理学研究科動物学専攻(主査)教授 岡田 節人, 教授 加藤 幹太, 教授 竹内 郁夫学位規則第5条第1項該当Kyoto UniversityDA

DEVELOPMENTAL ASPECTS OF STROBILATION IN AURELIA AURITA

Strolibation in Scyphozoa has been well known as a process to produce ephyrae. This process might include the basic aspect to understand the mechanism of cellular differentiation and transformation for the particular pattern of metamorphosis. We believe that the strobilation therefore seems to provide a unique opportunity for the study of growth and development, which has been pointed out by SPANGENBERG (1965). Although some known enviromental factors such as the lighting condition and the low temperature could initiate the strobilation (cf. recent review, PANGENBERG, 1968), we know little about the possible change which may occur in either the substantial or cellular level during the strobilation and the further metamorphic process. In this report, we are going to describe the morphological and physiological aspects of strobilation in Aurelia aurita