Foxr1, also known as FOXN5, is a member of the forkhead box (Fox) family of transcription factors. These factors are highly conserved and play essential roles in a wide range of cellular and developmental processes. Foxr1 has been associated with stress response pathways, brain development, early embryonic success, and is involved in certain cancers [1,2,3,4]. Genetic models, such as gene knockout models, have been crucial in understanding its functions.

In a mouse model, deletion of Foxr1 using Nuclease technology gene editing led to a severe survival deficit. Surviving newborn Foxr1 knockout mice had reduced body weight, decreased cortical thickness, and enlarged ventricles, suggesting its necessity for normal brain development [1]. In zebrafish, foxr1 -deficient females' embryos had a significantly lower survival rate, either failing to divide or undergoing abnormal division, indicating its role as a maternal-effect gene required for proper cell division and survival via the p21 and mTOR pathways [2]. In neuroblastoma, intrachromosomal deletion-fusions at 11q23 activate FOXR1, and RNAi silencing of FOXR1 strongly inhibited proliferation of osteosarcoma HOS cells and triggered apoptosis [3].

In conclusion, Foxr1 is essential for normal brain development and early embryonic success, and its dysregulation is involved in cancer, especially neuroblastoma. Gene knockout models in mice and zebrafish have been instrumental in revealing these functions, providing insights into disease mechanisms and potentially guiding future therapeutic strategies for related disorders.

References:

1. Mota, Andressa, Waxman, Hannah K, Hong, Rui, Beffert, Uwe, Ho, Angela. 2021. FOXR1 regulates stress response pathways and is necessary for proper brain development. In PLoS genetics, 17, e1009854. doi:10.1371/journal.pgen.1009854. https://pubmed.ncbi.nlm.nih.gov/34723967/

2. Cheung, Caroline T, Patinote, Amélie, Guiguen, Yann, Bobe, Julien. 2018. foxr1 is a novel maternal-effect gene in fish that is required for early embryonic success. In PeerJ, 6, e5534. doi:10.7717/peerj.5534. https://pubmed.ncbi.nlm.nih.gov/30155373/

3. Santo, E E, Ebus, M E, Koster, J, Versteeg, R, Molenaar, J J. 2011. Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma. In Oncogene, 31, 1571-81. doi:10.1038/onc.2011.344. https://pubmed.ncbi.nlm.nih.gov/21860421/

4. Katoh, Masuko, Igarashi, Maki, Fukuda, Hirokazu, Nakagama, Hitoshi, Katoh, Masaru. 2012. Cancer genetics and genomics of human FOX family genes. In Cancer letters, 328, 198-206. doi:10.1016/j.canlet.2012.09.017. https://pubmed.ncbi.nlm.nih.gov/23022474/