Prickle3-KO Mouse

Prickle3 is a gene with diverse functions. It is a vertebrate homologue of Drosophila Prickle and is involved in multiple biological pathways. It plays a role in establishing planar cell polarity (PCP), which is crucial for the coordinated orientation of cells in tissues. It also has functions related to cilia development, basal body organization, and is associated with the biogenesis of ATPase [2,3].

In the context of Leber's hereditary optic neuropathy (LHON), Prickle3 has been found to be a modifier gene. A specific X-linked mutation (c.157C>T, p.Arg53Trp) in Prickle3 encoding a mitochondrial protein was identified in Chinese families with LHON. This mutation acts in synergy with the ND4 11778G>A mitochondrial DNA mutation. Prickle3-deficient mice recapitulated LHON phenotypes, showing ATPase deficiencies, degeneration of retinal ganglion cells, and abnormal vasculature, demonstrating its role in the pathophysiology of LHON [1,4].

In summary, Prickle3 is essential for PCP establishment, cilia-related processes, and ATPase biogenesis. The study of Prickle3-deficient mouse models has provided valuable insights into its role in LHON, highlighting its significance in understanding the disease mechanism and potentially guiding future therapeutic strategies.

References:

1. Yu, Jialing, Liang, Xiaoyang, Ji, Yanchun, Jiang, Pingping, Guan, Min-Xin. . PRICKLE3 linked to ATPase biogenesis manifested Leber's hereditary optic neuropathy. In The Journal of clinical investigation, 130, 4935-4946. doi:10.1172/JCI134965. https://pubmed.ncbi.nlm.nih.gov/32516135/

2. Chuykin, Ilya, Itoh, Keiji, Kim, Kyeongmi, Sokol, Sergei Y. 2021. Frizzled3 inhibits Vangl2-Prickle3 association to establish planar cell polarity in the vertebrate neural plate. In Journal of cell science, 134, . doi:10.1242/jcs.258864. https://pubmed.ncbi.nlm.nih.gov/34806749/

3. Chu, Chih-Wen, Ossipova, Olga, Ioannou, Andriani, Sokol, Sergei Y. 2016. Prickle3 synergizes with Wtip to regulate basal body organization and cilia growth. In Scientific reports, 6, 24104. doi:10.1038/srep24104. https://pubmed.ncbi.nlm.nih.gov/27062996/

4. Nie, Zhipeng, Wang, Chenghui, Chen, Jiarong, Zhou, Xiangtian, Guan, Min-Xin. . Abnormal morphology and function in retinal ganglion cells derived from patients-specific iPSCs generated from individuals with Leber's hereditary optic neuropathy. In Human molecular genetics, 32, 231-243. doi:10.1093/hmg/ddac190. https://pubmed.ncbi.nlm.nih.gov/35947995/