C57BL/6JCya-Frmd5^em1/Cya

FRMD5, a FERM (four-point-one, ezrin, radixin, and moesin) domain-containing protein, localizes at cell adherens junctions, stabilizes cell-cell contacts, and is involved in regulating cell motility. It interacts with proteins like p120-catenin, integrin β5 subunit, and ROCK1, and may be part of pathways related to tumor progression and cell-matrix adhesion [3,4,5]. Genetic studies in model organisms can help understand its functions [3].

In mice, deficiency of FRMD5 leads to neurodevelopmental dysfunction and autistic-like behavior, with morphological neuron abnormalities, synaptic dysfunction, and learning and memory deficits [2]. In humans, de novo missense variants in FRMD5 are associated with childhood-onset ataxia, nystagmus, seizures, and developmental delay. Weighted gene co-expression network analysis (WGCNA) shows that FRMD5 belongs to gene networks involved in neurodevelopment and oligodendrocyte function [1,3]. A missense variant in FRMD5 also segregates with a novel autosomal dominant form of early-onset episodic nystagmus [6].

In summary, FRMD5 plays a crucial role in neurodevelopment and is associated with various neurological disorders. Studies on FRMD5-deficient mouse models have significantly contributed to understanding its role in these disease conditions, highlighting its importance in both normal biological processes and disease pathophysiology [1,2,3,6].

References:

1. Keller Sarmiento, Ignacio J, Bustos, Bernabe I, Blackburn, Joanna, Krainc, Dimitri, Mencacci, Niccolò E. 2024. De novo FRMD5 Missense Variants in Patients with Childhood-Onset Ataxia, Prominent Nystagmus, and Seizures. In Movement disorders : official journal of the Movement Disorder Society, 39, 1231-1236. doi:10.1002/mds.29791. https://pubmed.ncbi.nlm.nih.gov/38576116/

2. Lyu, Tian-Jie, Ma, Ji, Zhang, Xi-Yin, Wang, Yun, Zhang, Hong-Quan. 2024. Deficiency of FRMD5 results in neurodevelopmental dysfunction and autistic-like behavior in mice. In Molecular psychiatry, 29, 1253-1264. doi:10.1038/s41380-024-02407-w. https://pubmed.ncbi.nlm.nih.gov/38228891/

3. Lu, Shenzhao, Ma, Mengqi, Mao, Xiao, Dai, Yuwei, Bellen, Hugo J. . De novo variants in FRMD5 are associated with developmental delay, intellectual disability, ataxia, and abnormalities of eye movement. In American journal of human genetics, 109, 1932-1943. doi:10.1016/j.ajhg.2022.09.005. https://pubmed.ncbi.nlm.nih.gov/36206744/

4. Hu, Jinxia, Niu, Miaomiao, Li, Xueying, Zhan, Jun, Zhang, Hongquan. 2014. FERM domain-containing protein FRMD5 regulates cell motility via binding to integrin β5 subunit and ROCK1. In FEBS letters, 588, 4348-56. doi:10.1016/j.febslet.2014.10.012. https://pubmed.ncbi.nlm.nih.gov/25448675/

5. Wang, Tao, Pei, Xuelian, Zhan, Jun, Yu, Yu, Zhang, Hongquan. 2012. FERM-containing protein FRMD5 is a p120-catenin interacting protein that regulates tumor progression. In FEBS letters, 586, 3044-50. doi:10.1016/j.febslet.2012.07.019. https://pubmed.ncbi.nlm.nih.gov/22846708/

6. Hammar, Björn, Paulsson, Sofia, Helgadottir, Hafdis T, Sheikh, Rafi, Kvarnung, Malin. 2024. A Novel Type of Autosomal Dominant Episodic Nystagmus Segregating with a Variant in the FRMD5 Gene. In Neuro-ophthalmology (Aeolus Press), 48, 407-416. doi:10.1080/01658107.2024.2338562. https://pubmed.ncbi.nlm.nih.gov/39583022/