huOPA1 Mouse

The OPA1 gene (Mitochondrial Dynamin Like GTPase) is a nuclear-encoded gene that is ubiquitously expressed in human tissues, with particularly high levels in the retina (specifically retinal ganglion cells), brain, heart, and skeletal muscle. It encodes a large dynamin-related GTPase protein that exists as eight distinct isoforms due to alternative splicing; these are further processed into membrane-anchored long forms (L-OPA1) and soluble short forms (S-OPA1) ^[1]. This protein localizes to the inner mitochondrial membrane and the intermembrane space, where it plays a critical functional role in mediating mitochondrial fusion, maintaining the structural integrity of cristae, and regulating cytochrome c sequestration to prevent apoptosis ^[2]. Mutations in OPA1 are primarily associated with Autosomal Dominant Optic Atrophy (ADOA), the most common form of hereditary optic neuropathy characterized by the progressive degeneration of retinal ganglion cells and blindness, as well as more severe "ADOA-plus" syndromes and Behr syndrome, which include multisystemic symptoms such as sensorineural deafness, ataxia, peripheral neuropathy, and chronic progressive external ophthalmoplegia (CPEO) ^[3-4].

The huOPA1 mouse model was generated by replacing the sequence from upstream of exon 1 to downstream of 3’UTR of mouse Opa1 with the sequence from upstream of exon 1 to downstream of 3’UTR of human OPA1. This model is suitable for the study of Autosomal Dominant Optic Atrophy (ADOA), as well as for the development of OPA1-targeted therapies.