The hinge‐1 domain of Flna is not necessary for diverse physiological functions in mice

• DOI: 10.1111/eci.14308
• Publication Date: 2024-08-31T14:39:55Z
• Authors: Emma M. Wade; Elizabeth A. Goodin; Tim Morgan; Stephana Pereira; Adele G. Woolley; Zandra A. Jenkins; Philip B. Daniel; Stephen P. Robertson
• Keywords: FLNA

Abstract Introduction The filamins are cytoskeletal binding proteins that dynamically crosslink actin into orthogonal networks or bundle it stress fibres. domain structure of filamin is very well characterised, with an N‐terminal actin‐binding region, followed by 24 immunoglobulin‐like repeat units. domains separated distinct segments two regions low‐complexity known as hinge‐1 and hinge‐2. role especially has been proposed to be essential for protein function provides flexibility the otherwise rigid protein, a target cleavage calpain. Hinge‐1 protects cells from destructive forces, products calpain involved in critical cellular signalling processes, such survival during hypoxia. Pathogenic variants FLNA encoding Filamin A, including those remove domain, cause wide range survivable developmental disorders. In contrast, complete loss this gene embryonic lethal human mouse. Methods Results study, we show removing A mouse ( Flna ΔH1 ), while preserving its expression level leads no obvious phenotype. Detailed characterisation skeletons mice showed skeletal phenotype reminiscent found FLNA‐ causing dysplasia. Furthermore, nuclear functions maintained hinge‐1. Conclusion We conclude dispensable development over murine lifespan.