2011年2月
Increased globotriaosylceramide levels in a transgenic mouse expressing human alpha 1,4-galactosyltransferase and a mouse model for treating Fabry disease
JOURNAL OF BIOCHEMISTRY
- 巻
- 149
- 号
- 2
- 開始ページ
- 161
- 終了ページ
- 170
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/jb/mvq125
- 出版者・発行元
- OXFORD UNIV PRESS
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 alpha 1,4-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 mu g/mg protein, higher than in the TgM(+/-)/KO (< 0.1 mu g/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.
- リンク情報
- ID情報
-
- DOI : 10.1093/jb/mvq125
- ISSN : 0021-924X
- PubMed ID : 20961863
- Web of Science ID : WOS:000286474200006