Fabry disease is an inherited X-linked recessive metabolic disorder resulting from deficit activity of the lysosomal enzyme, alpha- galactosidase A (AGA). In affected hemizygous males, the progressive deposition of substrate in lysosomes of vascular endothelial and smooth muscle cells causes occlusive vascular disease. To date there is no specific treatment for this condition. Both enzyme replacement and gene therapy are under consideration, but carrying out these trials in human will be difficult and extremely time-consuming. An animal model for Fabry disease will be valuable to develop such therapeutic regimes. We have successfully disrupted AGA genomic locus in mouse embryonic stem cells by homologous recombination and generated mice heterozygous for AGA. These mice will be interbred to generate Fabry mice.
| Ohshima, T; Schiffmann, R; Murray, G J et al. (1999) Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice. Proc Natl Acad Sci U S A 96:6423-7 |
