Pygo1-KO Mouse

Pygo1, a homolog of Drosophila Pygo, is a core interaction factor in the Wnt/β -catenin signaling pathway [1,2,5,6,8]. This pathway is crucial in animal development and disease. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Pygo1's functions.

In mice, cardiac-specific overexpression of Pygo1 leads to pathological cardiac hypertrophy with declined cardiac function, which can be rescued by a β -catenin inhibitor. Also, in vivo down-regulation of Pygo1 during cardiac hypertrophic conditions antagonizes agonist-induced cardiac hypertrophy, indicating its role in regulating pathological cardiac hypertrophy in a β -catenin-dependent manner [1]. In human non-small-cell lung cancer (NSCLC) cells, overexpression of Pygo1 enhances cell proliferation, invasion, and migration via the Wnt/β -catenin pathway [2]. In human umbilical cord mesenchymal stromal/stem cells, overexpression of Pygo1 promotes differentiation into early cardiac lineage cells through activating the Wnt/β -catenin pathway [5]. Additionally, a genome-wide association study found that a Pygo1 single nucleotide polymorphism is associated with steatosis in non-alcoholic fatty liver disease, suggesting Wnt signalling pathways may be relevant in its pathogenesis [3]. A rare sarcoma case with an unusual fusion gene CBX6::KMT2A::PYGO1 was reported, though its significance needs further study [4]. Pygo1 was also among the genes upregulated by both exercise and calorie restriction in skeletal muscle, and its knockdown in C2C12 cells affected mitochondrial respiration [7]. In mouse kidney development, Pygo1 homozygous mutants were viable and fertile with no detectable defects, while double Pygo1/Pygo2 homozygous mutants showed disturbed ureteric bud and metanephric mesenchyme-derived compartments [6].

In conclusion, Pygo1 is an important regulator in the Wnt/β -catenin signaling pathway. Studies using KO/CKO mouse models and in vivo experiments have revealed its role in pathological cardiac hypertrophy, NSCLC, early cardiac lineage development, non-alcoholic fatty liver disease-related steatosis, and skeletal muscle response to exercise and calorie restriction. Understanding Pygo1's functions provides new insights into these biological processes and disease conditions.

References:

1. Lin, Li, Xu, Wei, Li, Yongqing, Fan, Xiongwei, Wu, Xiushan. 2021. Pygo1 regulates pathological cardiac hypertrophy via a β-catenin-dependent mechanism. In American journal of physiology. Heart and circulatory physiology, 320, H1634-H1645. doi:10.1152/ajpheart.00538.2020. https://pubmed.ncbi.nlm.nih.gov/33635162/

2. Wen, Yao, Li, Yuling, Yang, Boyu, Li, Fang, Yuan, Wuzhou. 2022. Pygo1 Regulates the Behavior of Human Non-Small-Cell Lung Cancer via the Wnt/β-Catenin Pathway. In Disease markers, 2022, 6993994. doi:10.1155/2022/6993994. https://pubmed.ncbi.nlm.nih.gov/36398031/

3. Anstee, Quentin M, Darlay, Rebecca, Cockell, Simon, Cordell, Heather J, Daly, Ann K. 2020. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort☆. In Journal of hepatology, 73, 505-515. doi:10.1016/j.jhep.2020.04.003. https://pubmed.ncbi.nlm.nih.gov/32298765/

4. Nakamura, Harumi, Kukita, Yoji, Wakamatsu, Toru, Yoshida, Keiichi, Yagi, Toshinari. 2023. KMT2A-rearranged sarcoma with unusual fusion gene CBX6::KMT2A::PYGO1. In Virchows Archiv : an international journal of pathology, 483, 891-897. doi:10.1007/s00428-023-03639-x. https://pubmed.ncbi.nlm.nih.gov/37713130/

5. Shen, Jie, Wu, Xiushan, Zhu, Ping, Wang, Yuequn, Zhao, Mingyi. 2022. Overexpression of PYGO1 promotes early cardiac lineage development in human umbilical cord mesenchymal stromal/stem cells by activating the Wnt/β-catenin pathway. In Human cell, 35, 1722-1735. doi:10.1007/s13577-022-00777-3. https://pubmed.ncbi.nlm.nih.gov/36085540/

6. Schwab, Kristopher R, Patterson, Larry T, Hartman, Heather A, Lin, Xinhua, Potter, S Steven. 2007. Pygo1 and Pygo2 roles in Wnt signaling in mammalian kidney development. In BMC biology, 5, 15. doi:. https://pubmed.ncbi.nlm.nih.gov/17425782/

7. Kang, Jae Sook, Kim, Min Ju, Kwon, Eun-Soo, Kwon, Ki-Sun, Yang, Yong Ryoul. 2023. Identification of novel genes associated with exercise and calorie restriction effects in skeletal muscle. In Aging, 15, 4667-4684. doi:10.18632/aging.204793. https://pubmed.ncbi.nlm.nih.gov/37310402/

8. Nakamura, Yoshihiro, Umehara, Takashi, Hamana, Hiroaki, Padmanabhan, Balasundaram, Yokoyama, Shigeyuki. 2007. Crystal structure analysis of the PHD domain of the transcription co-activator Pygopus. In Journal of molecular biology, 370, 80-92. doi:. https://pubmed.ncbi.nlm.nih.gov/17499269/