ArticleInternational journal of biological sciences2015
PKD1 mono-allelic knockout is sufficient to trigger renal cystogenesis in a mini-pig model.
Article in International journal of biological sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Deep Learning-Based Automated Cell Detection-Facilitated Meat Quality Evaluation.Foods (Basel, Switzerland) · 2024Article
- Cross-Species Insights into Autosomal Dominant Polycystic Kidney Disease: Provide an Alternative View on Research Advancement.International journal of molecular sciences · 2024Review
- Mechanisms of Cyst Development in Polycystic Kidney Disease.Advances in kidney disease and health · 2023Review
- Identification of osteopontin as a urinary biomarker for autosomal dominant polycystic kidney disease progression.Kidney research and clinical practice · 2022Article
- Review
- Generation of heterozygous PKD1 mutant pigs exhibiting early-onset renal cyst formation.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Establishment of transgenic pigs overexpressing humanFrontiers in genetics · 2022Article
- Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity.GeroScience · 2021Article
- Current status of the application of gene editing in pigs.The Journal of reproduction and development · 2021Review
- An Overview of In Vivo and In Vitro Models for Autosomal Dominant Polycystic Kidney Disease: A Journey from 3D-Cysts to Mini-Pigs.International journal of molecular sciences · 2020Review
- Monkeys mutant for PKD1 recapitulate human autosomal dominant polycystic kidney disease.Nature communications · 2019Article
- Genome editing in large animals: current status and future prospects.National science review · 2019Article
- The combination of metformin and 2-deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease.British journal of pharmacology · 2019Article
- Precision gene editing technology and applications in nephrology.Nature reviews. Nephrology · 2018Review
- Establishment and identification of cell lines from type O blood Korean native pigs and their efficiency in supporting embryonic development via somatic cell nuclear transfer.Journal of veterinary science · 2018Article
- Genetically engineered livestock for biomedical models.Transgenic research · 2016Review
- Gene targeting, genome editing: from Dolly to editors.Transgenic research · 2016Review
- Engineering large animal models of human disease.The Journal of pathology · 2016Review
- CRISPR-Cas9: from Genome Editing to Cancer Research.International journal of biological sciences · 2016Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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