Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Genetically modified mice have been used as animal models to recapitulate the pathology of human diseases for long time and been used for testing the efficacy of drugs. However, there are several cases that mice are not suitable for the recapitulation of human diseases.
Nonhuman primates (NHPs) are considered one of the most valuable animal models, because NHPs are closer to humans in organ size and anatomical structure, and therefore have higher potential to recapitulate human diseases, while difficult genetic manipulation is a major issue for creation of the disease models. So far, we have established techniques to create transgenic and genome editing cynomolgus monkeys. By using these techniques, we have explored an intractable human disease, Autosomal dominant polycystic kidney disease (ADPKD) with CRISPR/Cas9 technique, and demonstrated that homozygous disruption of PKD1 allele, a causative gene for ADPKD can result in the massive renal cyst development. We also have developed a technique to modify specific allele and generated PKD1 heterozygotes selectively. Importantly, the PKD1 heterozygotes exhibited renal cysts during fetal stages, showing the recapitulation of some of features of human ADPKD pathology.
