Gipc1-KO Mouse

Gipc1, also known as GAIP interacting protein, C terminus 1, is a multifunctional scaffold protein. It plays diverse roles in various biological processes, interacting with multiple proteins and being involved in different pathways. For instance, it binds to the C-terminus of β1 -adrenergic receptor, impacts lipid and cholesterol metabolism by interacting with SR -B1, and is associated with signaling pathways like PDGFR/PI3K/AKT [3,5,7].

In disease-related research, GIPC1 knockdown reduced MACC1-induced cell migration and invasion in colon cancer, and GIPC1 suppression decreased tumor growth and metastasis in mice transplanted with MACC1-overexpressing CRC cells, suggesting its role in cancer metastasis [1]. In gastric cancer, GIPC1 knockdown inhibited cell proliferation and migration by blocking the PDGFR/PI3K/AKT signaling pathway, while overexpression had the opposite effect, and in vivo, GIPC1 silencing decreased tumor growth and migration in nude mice [3]. In oculopharyngodistal myopathy (OPDM), an abnormal GGC repeat expansion in the 5' UTR of GIPC1 was identified in some patients, with altered mRNA levels [4]. In movement disorders, approximately 1% of patients might harbor GIPC1 CGG repeat expansion, which may lead to diseases related to intranuclear inclusions [2]. In breast cancer, high expression of GIPC1 in primary tumors was associated with a higher likelihood of bone metastasis and death in control patients, and zoledronate had a substantial effect in patients with high GIPC1 expression [6]. Also, overexpressing GIPC1 protected against pathological cardiac remodelling in mice as GIPC1 cKO mice showed spontaneous cardiac hypertrophy, fibrosis, and systolic dysfunction, while AAV9-mediated GIPC1 overexpression attenuated isoproterenol-induced pathological cardiac remodelling [5].

In conclusion, Gipc1 is involved in multiple biological functions and is closely associated with various diseases such as cancer, myopathies, movement disorders, and cardiac diseases. Gene knockout or knockdown models in mice have been crucial in revealing its functions in these disease conditions, providing valuable insights into disease mechanisms and potential therapeutic targets.

References:

1. Siegel, Franziska, Schmidt, Hannes, Juneja, Manisha, Schlag, Peter M, Stein, Ulrike. 2023. GIPC1 regulates MACC1-driven metastasis. In Frontiers in oncology, 13, 1280977. doi:10.3389/fonc.2023.1280977. https://pubmed.ncbi.nlm.nih.gov/38144523/

2. Fan, Yu, Shen, Si, Yang, Jing, Xu, Yuming, Shi, Changhe. 2022. GIPC1 CGG Repeat Expansion Is Associated with Movement Disorders. In Annals of neurology, 91, 704-715. doi:10.1002/ana.26325. https://pubmed.ncbi.nlm.nih.gov/35152460/

3. Li, Tingting, Zhong, Wei, Yang, Liu, Song, Gang, Luo, Fanghong. 2023. GIPC1 promotes tumor growth and migration in gastric cancer via activating PDGFR/PI3K/AKT signaling. In Oncology research, 32, 361-371. doi:10.32604/or.2023.043807. https://pubmed.ncbi.nlm.nih.gov/38186571/

4. Deng, Jianwen, Yu, Jiaxi, Li, Pidong, Hong, Daojun, Wang, Zhaoxia. 2020. Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy. In American journal of human genetics, 106, 793-804. doi:10.1016/j.ajhg.2020.04.011. https://pubmed.ncbi.nlm.nih.gov/32413282/

5. Sun, Xi, Han, Yanna, Yu, Yahan, Zhao, Dan, Bai, Yunlong. 2024. Overexpressing of the GIPC1 protects against pathological cardiac remodelling. In European journal of pharmacology, 971, 176488. doi:10.1016/j.ejphar.2024.176488. https://pubmed.ncbi.nlm.nih.gov/38458410/

6. Westbrook, Jules A, Cairns, David A, Peng, Jianhe, Coleman, Robert E, Brown, Janet E. 2016. CAPG and GIPC1: Breast Cancer Biomarkers for Bone Metastasis Development and Treatment. In Journal of the National Cancer Institute, 108, . doi:10.1093/jnci/djv360. https://pubmed.ncbi.nlm.nih.gov/26757732/

7. Zhang, Ziyu, Zhou, Qian, Liu, Rui, Guo, Zhigang, Hu, Zhigang. 2021. The adaptor protein GIPC1 stabilizes the scavenger receptor SR-B1 and increases its cholesterol uptake. In The Journal of biological chemistry, 296, 100616. doi:10.1016/j.jbc.2021.100616. https://pubmed.ncbi.nlm.nih.gov/33811857/