| First Author | Taguchi A | Year | 2013 |
| Journal | Biochem J | Volume | 456 |
| Issue | 3 | Pages | 373-83 |
| PubMed ID | 24094090 | Mgi Jnum | J:206001 |
| Mgi Id | MGI:5547645 | Doi | 10.1042/BJ20130825 |
| Citation | Taguchi A, et al. (2013) A symptomatic Fabry disease mouse model generated by inducing globotriaosylceramide synthesis. Biochem J 456(3):373-83 |
| abstractText | Fabry disease is a lysosomal storage disorder in which neutral glycosphingolipids, predominantly Gb3 (globotriaosylceramide), accumulate due to deficient alpha-Gal A (alpha-galactosidase A) activity. The GLAko (alpha-Gal A-knockout) mouse has been used as a model for Fabry disease, but it does not have any symptomatic abnormalities. In the present study, we generated a symptomatic mouse model (G3Stg/GLAko) by cross-breeding GLAko mice with transgenic mice expressing human Gb3 synthase. G3Stg/GLAko mice had high Gb3 levels in major organs, and their serum Gb3 level at 5-25 weeks of age was 6-10-fold higher than that in GLAko mice of the same age. G3Stg/GLAko mice showed progressive renal impairment, with albuminuria at 3 weeks of age, decreased urine osmolality at 5 weeks, polyuria at 10 weeks and increased blood urea nitrogen at 15 weeks. The urine volume and urinary albumin concentration were significantly reduced in the G3Stg/GLAko mice when human recombinant alpha-Gal A was administered intravenously. These data suggest that Gb3 accumulation is a primary pathogenic factor in the symptomatic phenotype of G3Stg/GLAko mice, and that this mouse line is suitable for studying the pathogenesis of Fabry disease and for preclinical studies of candidate therapies. |
