＜シンポジウム05―3＞筋ジストロフィー新規治療法開発の最前線
Largeによるα―ジストログリカノパチーに対する治療法の開発
斉藤 史明
帝京大学神経内科〔〒173―8605 東京都板橋区加賀2―11―1〕
The past decade of researches have revealed mutations of known or putative glycosyltransferases in several types of muscular dystrophy, including Fukuyama-type congenital muscular dystrophy. In these disorders, the function of α-dystroglycan is severely decreased, therefore they are called α-dystroglycanopathy. Recently, putative glycosyltransferase Large was shown to restore the defective function of α-dystroglycan, thus, it is an intriguing idea to apply this effect to the therapy of α-dystroglycanopathy. In the present study, we sought to test this possibility. Using several cultured cell lines, we confirmed that the overexpression of Large results in hyperglycosylation and marked enhancement of the function of α-dystroglycan. For this effect, the whole luminal domain of Large was shown to be necessary using several deletion constructs. We further generated transgenic mice overexpressing Large ubiquitously. In each tissue of the mice, the glycosylation of α-dystroglycan and its laminin binding activity was remarkably increased. Moreover, the morphological analyses on each tissue stained by H-E revealed no significant abnormality in the transgenic mice, suggesting no serious side effects by the overexpression of Large. Taken together, these results indicate that the restoration of the function of α-dystroglycan by Large should be an important molecular target to develop therapeutic strategies for α-dystroglycanopathy.
Full Text of this Article in Japanese PDF (610K)
(臨床神経, 51：918−921, 2011)
key words：筋ジストロフィー，α―ジストログリカノパチー，ジストログリカン，糖転移酵素，ラージ
（受付日：2011年5月19日）
