Foxp1, short for forkhead box protein P1, is a transcription factor crucial for the early development of many organ systems [5]. It participates in various biological processes and is involved in multiple pathways. Genetic models, such as knockout (KO) mouse models, are valuable for studying its functions.

In ovarian aging, FOXP1 emerges as a regulator that declines with age and inhibits CDKN1A transcription. Silencing FOXP1 in mice results in premature ovarian insufficiency, suggesting its importance in ovarian function [1]. In endothelial cells, endothelial-specific Foxp1 knockout (Foxp1ECKO) mice show increased atherosclerotic lesion formation, while endothelial-specific Foxp1 overexpression mice have reduced lesions. Foxp1 directly regulates endothelial inflammasome components, indicating its role in suppressing atherosclerosis [2]. In the context of FOXP1 syndrome caused by haploinsufficiency of the Foxp1 gene, Foxp1+/- mice exhibit mitochondrial dysfunction, oxidative stress, and subsequent cognitive and motor impairment [3]. Also, deficiency of FOXP1 in human embryonic stem cell-derived cardiomyocytes leads to hypertrophic and senescent phenotypes, suggesting its role in primate cardiac aging [4].

In conclusion, Foxp1 is essential for the normal development and function of multiple organ systems. Studies using KO/CKO mouse models have revealed its role in diseases like premature ovarian insufficiency, atherosclerosis, FOXP1 syndrome, and cardiac aging, providing insights into potential therapeutic targets for these conditions.

References:

1. Wu, Meng, Tang, Weicheng, Chen, Ying, Qiao, Huiying, Wang, Shixuan. 2024. Spatiotemporal transcriptomic changes of human ovarian aging and the regulatory role of FOXP1. In Nature aging, 4, 527-545. doi:10.1038/s43587-024-00607-1. https://pubmed.ncbi.nlm.nih.gov/38594460/

2. Zhuang, Tao, Liu, Jie, Chen, Xiaoli, Reilly, Muredach, Zhang, Yuzhen. 2019. Endothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation. In Circulation research, 125, 590-605. doi:10.1161/CIRCRESAHA.118.314402. https://pubmed.ncbi.nlm.nih.gov/31318658/

3. Wang, Jing, Fröhlich, Henning, Torres, Felipe Bodaleo, Agarwal, Amit, Rappold, Gudrun A. . Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome. In Proceedings of the National Academy of Sciences of the United States of America, 119, . doi:10.1073/pnas.2112852119. https://pubmed.ncbi.nlm.nih.gov/35165191/

4. Zhang, Yiyuan, Zheng, Yandong, Wang, Si, Ma, Shuai, Qu, Jing. . Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging. In Protein & cell, 14, 279-293. doi:10.1093/procel/pwac038. https://pubmed.ncbi.nlm.nih.gov/37084237/

5. Lozano, Reymundo, Gbekie, Catherine, Siper, Paige M, Buxbaum, Joseph D, Kolevzon, Alexander. 2021. FOXP1 syndrome: a review of the literature and practice parameters for medical assessment and monitoring. In Journal of neurodevelopmental disorders, 13, 18. doi:10.1186/s11689-021-09358-1. https://pubmed.ncbi.nlm.nih.gov/33892622/