title: Animal models for human polycystic kidney disease.
abstract: Polycystic kidney disease (PKD) is a hereditary disorder with abnormal cellular proliferation, fluid accumulation in numerous cysts, remodeling of extracellular matrix, inflammation, and fibrosis in the kidney and liver. The two major types of PKD show autosomal dominant (ADPKD) or autosomal recessive inheritance (ARPKD). ADPKD is one of the most common genetic diseases, with an incidence of 1:500-1,000. Approximately 50% of patients with ADPKD develop end-stage renal disease (ESRD) by the age of 60. On the other hand, ARPKD is relatively rare, with an incidence of approximately 1:20,000-40,000. ARPKD is diagnosed early in life, often prenatally. The gene products responsible for ADPKD and ARPKD distribute in primary cilia and are thought to control intercellular Ca(2+). Two types of animal model of PKD have been established: spontaneous hereditary models identified by the typical manifestations of PKD and gene-engineered models established by modification of human orthologous genes. Both types of animal models are used to study the mechanism of cystogenesis and efficacy of medical treatments. In PKD progression, critical roles of signaling pathways including MAPK, mTOR, and PPAR-γ have been discovered with these models. Therefore, experimental animal models are indispensable for investigating molecular mechanisms of PKD onset and progression as well as potential therapeutic treatments.
authors.affiliation: Education and Research Center of Animal Models for Human Diseases, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Nagao
authors.forename: Masanori
authors.initials: M
authors.lastname: Kugita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshihara
authors.forename: Tamio
authors.initials: T
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D018390:Gene Targeting; D006801:Humans; D051379:Mice; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D015398:Signal Transduction