Fxr1-KO Mouse

Fxr1, also known as Fragile X mental retardation autosomal 1, is an RNA-binding protein belonging to the Fragile X-related (FXR) family. It plays crucial roles in various biological processes, such as translational regulation, mRNA metabolism, and acts as a signaling scaffold. It is involved in pathways related to cell shape regulation, synaptic function, and spermatid development, and is important for normal development as its loss of function is intolerant in humans and lethal in neonatal mice [1,2,4]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

Germline-specific Fxr1 ablation in mice impaired the translation of target mRNAs, causing defective spermatid development and male infertility, indicating its essential role in spermiogenesis [1]. Point mutations in Fxr1, similar to those in its homolog FMR1 causing fragile X syndrome, disrupted the Fxr1 network, preventing actomyosin remodeling, which is vital for cell shape, migration, and synaptic function [2]. In Fxr1-related congenital myopathy, biallelic pathogenic variants in Fxr1 led to different phenotypes from severe infantile forms to milder adult-onset proximal muscle weakness [3].

In summary, Fxr1 is essential for processes like spermiogenesis, actomyosin remodeling, and muscle development. Mouse models with Fxr1 ablation or mutations have revealed its role in male infertility, congenital myopathy, and processes related to cell and synaptic functions, contributing to our understanding of these disease areas.

References:

1. Kang, Jun-Yan, Wen, Ze, Pan, Duo, Huang, Ying, Liu, Mo-Fang. 2022. LLPS of FXR1 drives spermiogenesis by activating translation of stored mRNAs. In Science (New York, N.Y.), 377, eabj6647. doi:10.1126/science.abj6647. https://pubmed.ncbi.nlm.nih.gov/35951695/

2. Chen, Xiuzhen, Fansler, Mervin M, Janjoš, Urška, Ule, Jernej, Mayr, Christine. 2024. The FXR1 network acts as a signaling scaffold for actomyosin remodeling. In Cell, 187, 5048-5063.e25. doi:10.1016/j.cell.2024.07.015. https://pubmed.ncbi.nlm.nih.gov/39106863/

3. Mroczek, Magdalena, Longman, Cheryl, Farrugia, Maria Elena, Straub, Volker, Yoon, Grace. 2022. FXR1-related congenital myopathy: expansion of the clinical and genetic spectrum. In Journal of medical genetics, 59, 1069-1074. doi:10.1136/jmedgenet-2021-108341. https://pubmed.ncbi.nlm.nih.gov/35393337/

4. Méndez-Albelo, Natasha M, Sandoval, Soraya O, Xu, Zhiyan, Zhao, Xinyu. 2024. An in-depth review of the function of RNA-binding protein FXR1 in neurodevelopment. In Cell and tissue research, 398, 63-77. doi:10.1007/s00441-024-03912-8. https://pubmed.ncbi.nlm.nih.gov/39155323/