| First Author | Shiozuka C | Year | 2011 |
| Journal | J Biochem | Volume | 149 |
| Issue | 2 | Pages | 161-70 |
| PubMed ID | 20961863 | Mgi Jnum | J:209274 |
| Mgi Id | MGI:5566898 | Doi | 10.1093/jb/mvq125 |
| Citation | Shiozuka C, et al. (2011) Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha1,4-galactosyltransferase and a mouse model for treating Fabry disease. J Biochem 149(2):161-70 |
| abstractText | Fabry disease is a lysosomal storage disorder caused by an alpha-galactosidase A (alpha-Gal A) deficiency and resulting in the accumulation of glycosphingolipids, predominantly globotriaosylceramide (Gb3). A transgenic mouse expressing the human alpha-Gal A R301Q mutant in an alpha-Gal A-knockout background (TgM/KO) should be useful for studying active-site-specific chaperone (ASSC) therapy for Fabry disease. However, the Gb3 content in the heart tissue of this mouse was too low to detect an ASSC-induced effect. To increase the Gb3 levels in mouse organs, we created transgenic mice (TgG3S) expressing human alpha1,4-galactosyltransferase (Gb3 synthase). High levels of Gb3 were observed in all major organs of the TgG3S mouse. A TgG3S (+/-)M(+/-)/KO mouse was prepared by cross-breeding the TgG3S and TgM/KO mice and the Gb3 content in the heart of the TgG3S(+/-)M(+/-)/KO mouse was 1.4 microg/mg protein, higher than in the TgM(+/-)/KO (<0.1 microg/mg protein). Treatment with an ASSC, 1-deoxygalactonojirimycin, caused a marked induction of alpha-Gal A activity and a concomitant reduction of the Gb3 content in the TgG3S(+/-) M(+/-)/KO mouse organs. These data indicated that the TgG3S(+/-) M(+/-)/KO mouse was suitable for studying ASSC therapy for Fabry disease, and that the TgG3S mouse would be useful for studying the effect of high Gb3 levels in mouse organs. |
