huUSH2A(E10-15)-c.2282_2288delCTCACTC Mouse

Usher syndrome (USH), also known as hereditary deafness-retinitis pigmentosa syndrome or retinitis pigmentosa-sensorineural deafness syndrome, is a genetically heterogeneous autosomal recessive disorder. Patients typically present with congenital sensorineural hearing loss, progressive retinitis pigmentosa (RP), and visual impairment. USH represents the most prevalent cause of combined deafness and blindness, with an estimated incidence ranging from 1 in 5,000 to 1 in 16,000. Based on age of onset and involvement of auditory and vestibular function, USH is clinically classified into three subtypes: type I (USH1), type II (USH2), and type III (USH3). USH1 is characterized by profound congenital deafness, vestibular dysfunction, and RP onset before adulthood. USH2 patients exhibit mild-to-moderate hearing loss without vestibular impairment, with RP symptoms typically emerging in adulthood. USH3 patients have normal hearing at birth, followed by progressive hearing loss and RP. Among these, USH1 is the most severe, whereas USH2 is the most prevalent, each accounting for approximately 40–50% of cases. Due to underdiagnosis and variable disease progression, the actual prevalence of USH2 may exceed current estimates.

USH2A is the principal causative gene for USH2, with approximately 75–90% of USH2 patients harboring pathogenic variants in USH2A ^[1]. The USH2A gene encodes usherin, a basement membrane-associated protein containing laminin EGF-like domains, a pentraxin domain, and multiple fibronectin type III motifs. Usherin is predominantly expressed in the basement membrane and plays a critical role in the development and homeostasis of the inner ear and retina. In cochlear hair cells, usherin is essential for morphogenesis and auditory signal transduction, while in the retinal basement membrane, it regulates adhesion through interactions with fibronectin. Mutations in USH2A disrupt normal hair cell development and maintenance, impair fibronectin assembly in the retinal basement membrane, and compromise adhesion, collectively contributing to hearing loss and RP pathology. Exon 13 of USH2A is a mutational hotspot, with c.2299delG and c.2276G>T being the most common pathogenic variants. Multiple therapeutic programs are currently focused on this region ^{[2-4, 6]}.

The huUSH2A(E10-15)-c.2282_2288delCTCACTC mouse model was generated by introducing a human USH2A exon 13 deletion (bases 2282–2288, CTCACTC) into the huUSH2A(E10-15) background (catalog ID: C001554). This model enables mechanistic studies and preclinical evaluation of candidate therapeutics for Usher syndrome. Furthermore, leveraging proprietary TurboKnockout technology integrated with BAC recombination, Cyagen Biosciences offers customizable model generation services targeting diverse mutations to support pharmacodynamic and translational research in Usher syndrome.