Phenotypes and genetic etiology of spontaneous polycystic kidney and liver disease in cynomolgus monkey

Ruo Wu; Bing Bai; Feng Li; Raoxian Bai; Yan Zhuo; Zhengna Zhu; Rongfang Jia; Shangang Li; Yongchang Chen; Xiaoping Lan

doi:10.3389/fvets.2023.1106016

Phenotypes and genetic etiology of spontaneous polycystic kidney and liver disease in cynomolgus monkey

Front Vet Sci. 2023 Feb 16:10:1106016. doi: 10.3389/fvets.2023.1106016. eCollection 2023.

Authors

Ruo Wu^{1

2}, Bing Bai^{1

2}, Feng Li³, Raoxian Bai^{1

2}, Yan Zhuo^{1

2}, Zhengna Zhu^{1

2}, Rongfang Jia^{1

2}, Shangang Li^{1

2}, Yongchang Chen^{1

2}, Xiaoping Lan⁴

Affiliations

¹ State Key Laboratory of Primate Biomedical Research and Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, China.
² Yunnan Key Laboratory of Primate Biomedical Research, Kunming, China.
³ Kunming Biomed International, Kunming, China.
⁴ Molecular Diagnostic Laboratory, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Introduction: Polycystic kidney disease (PKD) is a common autosomal dominant or recessive genetic disease, often accompanied by polycystic liver disease (PLD). Many cases of PKD in animals have been reported. However, little is known about the genes that cause PKD in animals.

Methods: In this study, we evaluated the clinical phenotypes of PKD in two spontaneously aged cynomolgus monkeys and explored the genetic etiology using whole-genome sequencing (WGS). Ultrasonic and histological consequences were further investigated in PKD- and PLD-affected monkeys.

Results: The results indicated that the kidneys of the two monkeys had varying degrees of cystic changes, and the renal cortex was thinned and accompanied by fluid accumulation. As for hepatopathy, inflammatory cell infiltration, cystic effusion, steatosis of hepatocytes, and pseudo-lobular were found. Based on WGS results, the variants of PKD1:(XM_015442355: c.1144G>C p. E382Q) and GANAB: (NM_001285075.1: c.2708T>C/p. V903A) are predicted to be likely pathogenic heterozygous mutations in PKD- and PLD-affected monkeys.

Discussion: Our study suggests that the cynomolgus monkey PKD and PLD phenotypes are very similar to those in humans, and are probably caused by pathogenic genes homologous to humans. The results indicate that cynomolgus monkeys can be used as the most appropriate animal model for human PKD pathogenesis research and therapeutic drug screening.

Keywords: cynomolgus monkey; genetic etiology; phenotype; polycystic kidney disease; polycystic liver disease; whole-genome sequencing.

Grants and funding

This work was supported by the National Key Research and Development Program of China (grant numbers: 2018YFA0107902 and 2018YFA0801403) and the Natural Science Foundation of Yunnan Province (subtitle: major basic research project) (grant numbers: 202001BC070001 and 202102AA100053).