Gla KO Mouse

Fabry Disease (FD) is a rare genetic lysosomal storage disorder caused by mutations in the GLA gene on the X chromosome, leading to a deficiency in lysosomal α-galactosidase A (α-GalA) activity. The absence of α-GalA results in the accumulation of the metabolic substrate globotriaosylceramide (GL3) in multiple organs, ultimately causing organ damage. In severe cases, this may lead to cardiovascular complications, end-stage renal disease, and even early death ^[1]. Clinically, FD is divided into early-onset (typical) and late-onset (attenuated) forms. Early-onset patients almost completely lose α-GalA activity and experience multi-organ damage early in life, while late-onset patients retain some enzyme activity, with symptom severity dependent on the residual enzyme activity ^[1-2]. Since the GLA gene is located on the X chromosome, male patients typically experience more severe symptoms. Current treatment options include enzyme replacement therapy (ERT) and molecular chaperone therapy (migalastat), but due to high costs and various limitations on efficacy, new therapeutic strategies are urgently needed ^[3]. In preclinical studies, Gla knockout (KO) mice have become the "gold standard" for studying the mechanisms of FD and evaluating therapies ^[4]. Gla KO mice exhibit GL3 accumulation in various tissues with aging, and their histological changes closely mimic the pathological features seen in human FD patients. It is widely used in research on enzyme replacement therapy, AAV gene therapy, and substrate reduction therapy ^[5-13].

This strain is a Gla gene knockout (KO) mouse model of Fabry Disease, created using gene editing technology to knockout the Gla gene on the X chromosome of mice (the homolog of the human GLA gene). The deletion of the Gla gene results in the absence of Gla gene expression and α-GalA activity. This model can be widely used for studying the mechanisms of Fabry Disease, assessing the efficacy and safety of potential therapies, and investigating lysosomal-related metabolic disorders and their pathophysiological effects.