{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:53:30Z","timestamp":1791114810486,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,9,2]],"date-time":"2010-09-02T00:00:00Z","timestamp":1283385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2010,11]]},"abstract":"Abstract<\/jats:title>\n \n Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common life\u2010threatening inherited diseases, and the\n PKD1<\/jats:italic>\n gene is responsible for most cases of this disease. Previous efforts to establish a mouse model that recapitulates the phenotypic characteristics of ADPKD, which have used conventional or conditional knockout of the mouse orthologue\n Pkd1<\/jats:italic>\n , have been unsuccessful or unreliable. In a previous study, we described the generation of a novel\n Pkd1<\/jats:italic>\n hypomorphic allele, in which\n Pkd1<\/jats:italic>\n expression was significantly reduced but not totally blocked. These\n Pkd1<\/jats:italic>\n homozygous mutant mice rapidly developed renal cystic disease, supporting the hypothesis that \u2018haploinsufficiency\u2019 explains development of the ADPKD phenotype. In the present study, we further investigated the\n Pkd1<\/jats:italic>\n haploinsufficiency effect by generating\n Pkd1<\/jats:italic>\n knockdown transgenic mice with co\u2010cistronic expression of two miRNA hairpins specific to\n Pkd1<\/jats:italic>\n transcript and an Emerald GFP reporter driven by a human ubiquitin B promoter. Two transgenic lines which had \u223c60\u201370% reduction of\n Pkd1<\/jats:italic>\n expression developed severe renal cystic disease at a rate similar to that of human ADPKD. These results further support the haploinsufficiency hypothesis, and suggest that the onset and progression of the renal cystic diseases are correlated with the level of\n Pkd1<\/jats:italic>\n expression. The two novel mutant lines of mice appear to be ideal models for the study of ADPKD. Copyright \u00a9 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.2765","type":"journal-article","created":{"date-parts":[[2010,8,28]],"date-time":"2010-08-28T14:43:18Z","timestamp":1283006598000},"page":"238-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against\n 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