{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:54:49Z","timestamp":1791114889612,"version":"4.1.0"},"reference-count":54,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>\n                    Development of novel therapies for polycystic kidney disease (PKD) requires assays that adequately reflect disease biology and are adaptable to high-throughput screening. Here we describe an embryonic cystic kidney organ culture model and demonstrate that a new mutant allele of the Pkd1 gene ( Pkd1\n                    <jats:sup>tm1Bdgz<\/jats:sup>\n                    ) modulates cystogenesis in this model. Cyst formation induced by cAMP is influenced by the dosage of the mutant allele: Pkd1\n                    <jats:sup>tm1Bdgz<\/jats:sup>\n                    \u2212\/\u2212 cultures develop a larger cystic area compared with +\/+ counterparts, while Pkd1\n                    <jats:sup>tm1Bdgz<\/jats:sup>\n                    +\/\u2212 cultures show an intermediate phenotype. A similar relationship between the degree of cystogenesis and mutant gene dosage is seen in cystic kidney organ cultures derived from mice with a mutated Nek8 gene ( Nek8\n                    <jats:sup>jck<\/jats:sup>\n                    ). Both Pkd1\u2212 and Nek8\u2212 cultures display altered cell-cell junctions, with reduced E-cadherin expression and altered desmosomal protein expression, similar to ADPKD epithelia. Additionally, characteristic ciliary abnormalities are identified in cystic kidney cultures, with elevated ciliary polycystin 1 expression in Nek8 homozygous cultures and elevated ciliary Nek8 protein expression in Pkd1 homozygotes. These data suggest that the Nek8 and Pkd1 genes function in a common pathway to regulate cystogenesis. Moreover, compound Pkd1 and Nek8 heterozygous adult mice develop a more aggressive cystic disease than animals with a mutation in either gene alone. Finally, we validate the kidney organ culture cystogenesis assay as a therapeutic testing platform using the CDK inhibitor roscovitine. Therefore, embryonic kidney organ culture represents a relevant model for studying molecular cystogenesis and a rapid tool for the screening for therapies that block cystic growth.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00362.2007","type":"journal-article","created":{"date-parts":[[2007,10,10]],"date-time":"2007-10-10T20:54:07Z","timestamp":1192049647000},"page":"F73-F83","source":"Crossref","is-referenced-by-count":43,"title":["<i>Pkd1<\/i>\n                    and\n                    <i>Nek8<\/i>\n                    mutations affect cell-cell adhesion and cilia in cysts formed in kidney organ cultures"],"prefix":"10.1152","volume":"294","author":[{"given":"Thomas A.","family":"Natoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany C.","family":"Gareski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Dackowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay O.","family":"Bukanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herv\u00e9","family":"Husson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Piepenhagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oxana","family":"Ibraghimov-Beskrovnaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","unstructured":"Avner ED\n                      , Piesco NP, Sweeney WE Jr, Studnicki FM, Fetterman GH, Ellis D.\n                      Hydrocortisone-induced cystic metanephric maldevelopment in serum-free organ culture.\n                      Lab Invest\n                      50\n                      : 208\u2013218, 1984."},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01960636"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1007\/BF01952400"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1007\/BF01975904"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1097\/00041552-199707000-00012"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.211191098"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-328"},{"key":"R8","unstructured":"Brown T\n                      , Mackey K, Du T.\n                      Analysis of RNA by Northern and slot blot hybridization. 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