title: Cyst expansion and regression in a mouse model of polycystic kidney disease.
abstract: Autosomal-dominant polycystic kidney disease is characterized by progressive cyst formation and fibrosis in the kidneys. Here we describe an orthologous Pkd1(nl,nl) mouse model, with reduced expression of the normal Pkd1 transcript, on a fixed genetic background of equal parts C57Bl/6 and 129Ola/Hsd mice (B6Ola-Pkd1(nl,nl)). In these mice, the first cysts develop from mature proximal tubules around birth. Subsequently, larger cysts become visible at day 7, followed by distal tubule and collecting duct cyst formation, and progressive cystic enlargement to develop into large cystic kidneys within 4 weeks. Interestingly, cyst expansion was followed by renal volume regression due to cyst collapse. This was accompanied by focal formation of fibrotic areas, an increased expression of genes involved in matrix remodeling and subsequently an increase in infiltrating immune cells. After an initial increase in blood urea within the first 4 weeks, renal function remained stable over time and the mice were able to survive up to a year. Also, in kidneys of ADPKD patients collapsed cysts were observed, in addition to massive fibrosis and immune infiltrates. Thus, B6Ola-Pkd1(nl,nl) mice show regression of cysts and renal volume that is not accompanied by a reduction in blood urea levels.
authors: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors: Hester
authors: H
authors: Happé
authors: Annemieke M
authors: AM
authors: van der Wal
authors: Daniela C F
authors: DC
authors: Salvatori
authors: Wouter N
authors: WN
authors: Leonhard
authors: Martijn H
authors: MH
authors: Breuning
authors: Emile
authors: E
authors: de Heer
authors: Dorien J M
authors: DJ
authors: Peters
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism; D014508:Urea / Q000097:blood
chemical_list: D015415:Biomarkers; D050396:TRPP Cation Channels; D014508:Urea