PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis in a mini-pig model

International Journal of Biological Sciences
Jin HeNing Li

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 ...Continue Reading

Citations

Sep 29, 2015·The Journal of Pathology·C Bruce A WhitelawBhanu P Telugu
Jan 29, 2016·Transgenic Research·Christopher S Rogers
Aug 10, 2018·Nature Reviews. Nephrology·Zachary WareJoncasStephen C Ekker
Feb 6, 2016·Transgenic Research·Wenfang TanC Bruce A Whitelaw
Dec 12, 2019·Nature Communications·Tomoyuki TsukiyamaMasatsugu Ema
Jul 8, 2020·International Journal of Molecular Sciences·Svenja KoslowskiLaurent Meijer
Apr 13, 2021·The Journal of Reproduction and Development·Fuminori TaniharaTakeshige Otoi

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BETA
transgenic
transfection
biopsies
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