title: PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis in a mini-pig model.
abstract: PKD1 and PKD2 mutations could lead to autosomal dominant polycystic kidney disease (ADPKD), which afflicts millions of people worldwide. Due to the marked differences in the lifespan, size, anatomy, and physiology from humans, rodent ADPKD models cannot fully mimic the disease. To obtain a large animal model that recapitulates the disease, we constructed a mini-pig model by mono-allelic knockout (KO) of PKD1 using zinc finger nuclease. The mono-allelic KO pigs had lower PKD1 expression than their wild-type littermates at both the transcriptional and translational levels. After approximately six months, renal cysts appeared and grew progressively in the KO pigs. Histological analysis showed that renal cysts were scatteredly distributed in the mutant pig kidneys and were lined by either cuboidal or flattened epithelial cells. Contrast-enhanced computed tomography confirmed that all of the mutant pigs had renal and hepatic cysts, when they were 11-month-old. Immunohistochemical analysis revealed that most of the cysts were derived from the proximal tubules and collecting ducts. Therefore, the PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis, and this pig model may provide a platform for future study of renal cyst formation.
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China ; 2. College of Animal Science and Technology, China Agricultural University, Beijing, PR China.
authors: Jin
authors: J
authors: He
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Qiuyan
authors: Q
authors: Li
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Suyun
authors: S
authors: Fang
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Ying
authors: Y
authors: Guo
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Tongxin
authors: T
authors: Liu
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Jianhua
authors: J
authors: Ye
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Zhengquan
authors: Z
authors: Yu
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Ran
authors: R
authors: Zhang
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Yaofeng
authors: Y
authors: Zhao
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China.
authors: Xiaoxiang
authors: X
authors: Hu
authors: 3. Department of Nephrology, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing, PR China.
authors: Xueyuan
authors: X
authors: Bai
authors: 3. Department of Nephrology, State Key Laboratory of Kidney Disease, Chinese PLA General Hospital, Beijing, PR China.
authors: Xiangmei
authors: X
authors: Chen
authors: 1. State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, PR China ; 4. College of Animal Science and Technology, Yunnan Agricultural University, Kunming, PR China.
authors: Ning
authors: N
authors: Li
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D050396:TRPP Cation Channels
keywords: ADPKD; Disease model; PKD1; ZFN