Transgenic rescue of Krabbe disease in the twitcher mouse

被引：20

作者：

De Gasperi, R

Friedrich, VL

Perez, GM

Senturk, E

Wen, PH

Kelley, K

Elder, GA

Sosa, MAG

机构：

[1] Vet Adm Med Ctr, Bronx, NY 10468 USA

[2] NYU, Mt Sinai Sch Med, Dept Psychiat, New York, NY USA

[3] NYU, Mt Sinai Sch Med, Dept Neurobiol, New York, NY USA

[4] NYU, Mt Sinai Sch Med, Dept Mol Cell & Dev Biol, New York, NY USA

[5] NYU, Mt Sinai Sch Med, Mouse Genet Shared Res Facil, New York, NY USA

来源：

GENE THERAPY | 2004年 / 11卷 / 15期

关键词：

D O I：

10.1038/sj.gt.3302282

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The twitcher mouse is a natural model of Krabbe disease caused by galactocerebrosidase (GALC) deficiency. Previous attempts at rescuing the twitcher mouse by bone marrow transplantion, viral transduction, or transgenesis were only partially successful. Here, we report the transgenic (tg) rescue of the twitcher mouse with a BAC clone harboring the entire GALC. The twi/twi/hGALC tg mice exhibited growth, motor function, and fertility similar to those of nonaffected animals. These animals had normal levels of GALC activity in brain and were free of the typical twitcher demyelinating pathology. Surprisingly, GALC expression in twi/twi hGALC tg kidneys was low and galactocerebroside storage was only partially cleared. Nonetheless, these mice have been maintained for over 1 year without any sign of disease. Since pathological damage associated with GALC deficiency is confined to the nervous system, our work represents the first successful rescue of the twitcher mouse and opens the possibility of developing novel therapeutic approaches.

引用

页码：1188 / 1194

页数：7

共 31 条

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