Title:

Human Disease Modeling with Genetically-Engineered Cynomolgus Monkeys

 

Speaker:

Masatsugu Ema, PhD

Department of Stem Cells and Human Disease Models

Research Center for Animal Life Science, Shiga University of Medical Science

 

Abstract:

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 may have higher potential to recapitulate human diseases, while difficult genetic manipulation is a major obstacle for creation of human disease models. So far, we have established lentivirus-mediated techniques to generate transgenic (Tg) cynomolgus monkeys and created Tg monkeys overexpressing Amyloid beta Precursor Protein with the Alzheimer’s disease mutations. We also have established efficient genome editing technique in cynomolgus monkeys with CRISPR/Cas9, and explored an intractable human disease, Autosomal dominant polycystic kidney disease (ADPKD). We found that homozygous disruption of PKD1 allele, a causative gene for ADPKD can result in the massive renal cyst development, while PKD1 heterozygotes exhibited renal cysts during fetal stages, showing the recapitulation of some of features of human ADPKD pathology. I would like to talk about recent progress and future direction on development of genetically engineered NHPs and its application to human disease modeling.

 

References:

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Seita Y et a., J Alzheimers Dis 75 (1): 45-60. (2020)

Kobayashi K et al., Stem Cell Res. 37:101439. (2019)

Tsukiyama T et al., Nat. Commun 10(1):5517. (2019)