Filamin B (FLNB), an actin-binding protein, is crucial for skeletal development and is likely involved in pathways related to cell-cell adhesion, migration, and tissue morphogenesis [1,2,3,4]. Its proper function is of overall biological importance, especially in processes like bone formation and palatal development. Genetic models, such as gene-knockout (KO) mouse models, have been valuable in studying FLNB.

In a mouse model with a pathogenic point mutation in FLNB (NM_001081427.1: c.4756G > A (p.Gly1586Arg)), there were fusions in tarsal bones, indicating interference with skeletal segmentation. This was associated with down-regulation of HOXD10 and HOXB2 transcription levels in specific regions of the embryo, suggesting that loss-of-function mutations in FLNB may lead to abnormal skeletal segmentation via HOX gene regulation [4]. In addition, Flnb-/-embryos display cleft palates and skeletal defects, revealing that FLNB is required for palate development in mice [1].

Overall, FLNB plays essential roles in skeletal and palatal development. Studies using KO mouse models have significantly contributed to understanding its function in these processes. Moreover, FLNB may have implications in various disease conditions, such as non-syndromic orofacial clefts and spondylocarpotarsal synostosis syndrome, highlighting its importance in human health and disease research [1,2,3].

References:

1. Huang, Wenbin, Zhang, Shiying, Lin, Jiuxiang, Zhao, Huaxiang, Chen, Feng. 2023. Rare loss-of-function variants in FLNB cause non-syndromic orofacial clefts. In Journal of genetics and genomics = Yi chuan xue bao, 51, 222-229. doi:10.1016/j.jgg.2023.03.012. https://pubmed.ncbi.nlm.nih.gov/37003352/

2. Shahid, Hamna, Shakoor, Nazish, Bibi, Anisa, Malik, Sajid, Mumtaz, Sara. 2023. A Stop-gain Variant c.220C>T (p.(Gln74*)) in FLNB Segregates with Spondylocarpotarsal Synostosis Syndrome in a Consanguineous Family. In The Yale journal of biology and medicine, 96, 383-396. doi:10.59249/UTCP9818. https://pubmed.ncbi.nlm.nih.gov/37781000/

3. Ramos-Mejía, R, Del Pino, M, Aza-Carmona, M, Heath, K E, Fano, V. 2022. Novel FLNB Variants in Seven Argentinian Cases with Spondylocarpotarsal Synostosis Syndrome. In Journal of pediatric genetics, 13, 167-174. doi:10.1055/s-0042-1759782. https://pubmed.ncbi.nlm.nih.gov/39086440/

4. Xu, Qiming, Cui, Lijia, Lin, Yude, Cui, Leigh-Anne, Xia, Weibo. 2024. Disruption of FLNB leads to skeletal malformation by interfering with skeletal segmentation through the HOX gene. In Bone reports, 20, 101746. doi:10.1016/j.bonr.2024.101746. https://pubmed.ncbi.nlm.nih.gov/38463381/