Related Experiment Video
Updated: Jan 2, 2026
Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
Published on: September 1, 2015
Monkeys mutant for PKD1 recapitulate human autosomal dominant polycystic kidney disease
Tomoyuki Tsukiyama1,2, Kenichi Kobayashi3,4, Masataka Nakaya3,5
1Department of Stem Cells and Human Disease Models, Research Center for Animal Life Science, Shiga University of Medical Science, Shiga, 520-2192, Japan. ttsuki@belle.shiga-med.ac.jp.
Abstract:
Autosomal dominant polycystic kidney disease (ADPKD) caused by PKD1 mutations is one of the most common hereditary disorders. However, the key pathological processes underlying cyst development and exacerbation in pre-symptomatic stages remain unknown, because rodent models do not recapitulate critical disease phenotypes, including disease onset in heterozygotes. Here, using CRISPR/Cas9, we generate ADPKD models with PKD1 mutations in cynomolgus monkeys. As in humans and mice, near-complete PKD1 depletion induces severe cyst formation mainly in collecting ducts. Importantly, unlike in mice, PKD1 heterozygote monkeys exhibit cyst formation perinatally in distal tubules, possibly reflecting the initial pathology in humans. Many monkeys in these models survive after cyst formation, and cysts progress with age. Furthermore, we succeed in generating selective heterozygous mutations using allele-specific targeting. We propose that our models elucidate the onset and progression of ADPKD, which will serve as a critical basis for establishing new therapeutic strategies, including drug treatments.
Insights
New monkey models reveal early cyst development in autosomal dominant polycystic kidney disease (ADPKD). These models mimic human disease progression, offering new avenues for therapeutic strategies against this common hereditary disorder.
Area of Science:
- Nephrology
- Genetics
- Animal Models
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary kidney disorder caused by PKD1 mutations.
- Current rodent models do not fully recapitulate ADPKD phenotypes, limiting understanding of early pathological processes.
Purpose of the Study:
- To develop novel animal models that accurately reflect ADPKD pathogenesis, particularly in pre-symptomatic stages.
- To investigate the initial cyst development and progression of ADPKD.
Main Methods:
- CRISPR/Cas9 gene editing was used to create PKD1 mutations in cynomolgus monkeys.
- Generated models with near-complete PKD1 depletion and selective heterozygous mutations.
Main Results:
- PKD1-mutated monkeys showed cyst formation, primarily in collecting ducts (near-complete depletion) and perinatally in distal tubules (heterozygotes).
- Heterozygote monkey models exhibit early cyst formation, potentially mirroring human ADPKD onset.
- Observed cyst progression with age in surviving models.
Conclusions:
- Cynomolgus monkey models with PKD1 mutations provide a valuable platform for studying ADPKD onset and progression.
- These models can facilitate the development of new therapeutic strategies for ADPKD.
More Related Videos
07:35Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
12:47Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
Published on: February 3, 2012
