This technology includes an alpha-galactosidase-A knockout mouse model that can be used to study Fabry disease, an X-linked lysosomal storage disorder. Alpha-galactosidase-A is a crucial enzyme responsible for the breakdown of glycolipids, particularly globotriaosylceramide (Gb3), within lysosomes. In Fabry disease, a rare and inherited lysosomal storage disorder, mutations in the GLA gene lead to deficient or non-functional alpha-galactosidase-A enzyme activity. This enzymatic deficiency results in the progressive accumulation of Gb3 and related glycolipids in various cells and tissues, causing multisystemic manifestations such as renal dysfunction, cardiac abnormalities, neuropathic pain, and skin lesions. This invention, an alpha-galactosidase-A knockout mouse model, serves as a platform for preclinical trials, enabling the evaluation of novel enzyme replacement therapies, substrate reduction therapies, and gene therapy approaches.