Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells.
Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells.
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溶酶体疾病半乳糖唾液酸贮积症的小鼠模型以及通过过度表达红系前体细胞校正表型。
DOI：
10.1101/gad.9.21.2623
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发表时间：
1995
影响因子：
10.5
通讯作者：
A. d’Azzo
中科院分区：
文献类型：
--
作者：
X. Zhou;H. Morreau;R. Rottier;D. Davis;E. Bonten;N. Gillemans;D. Wenger;F. Grosveld;P. Doherty;K. Suzuki;G. Grosveld;A. d’Azzo
溶酶体贮积症半乳糖唾液酸贮积症是由于保护性蛋白/组织蛋白酶 A (PPCA) 的原发性缺乏所致，这反过来会影响 β-半乳糖苷酶和神经氨酸酶的活性。 PPCA 基因座无效突变的纯合小鼠在出生后不久就会出现该疾病的症状，并形成与患有半乳糖唾液酸贮积症的人类患者非常相似的表型。它们的大多数组织表现出特定细胞的特征性空泡化，这归因于溶酶体储存。尿液中唾液酸寡糖的过量排泄是该疾病的诊断依据。受影响的小鼠由于严重的器官功能障碍（尤其是肾脏功能障碍）而逐渐恶化。通过用来自在红系前体细胞中过表达人 PPCA 的转基因系的骨髓移植无效突变体，可以纠正缺陷的表型。转基因骨髓比正常骨髓对内脏器官进行更有效和更彻底的矫正。我们的数据证明了这种与人类疾病非常相似的动物模型对于试验旨在将功能蛋白或基因传递到受影响器官的治疗策略的有用性。此外，他们还提出了使用经过改造的骨髓细胞过度表达和分泌校正溶酶体蛋白来治疗半乳糖唾液酸贮积症和其他疾病的可行性。
The lysosomal storage disorder galactosialidosis results from a primary deficiency of the protective protein/cathepsin A (PPCA), which in turn affects the activities of beta-galactosidase and neuraminidase. Mice homozygous for a null mutation at the PPCA locus present with signs of the disease shortly after birth and develop a phenotype closely resembling human patients with galactosialidosis. Most of their tissues show characteristic vacuolation of specific cells, attributable to lysosomal storage. Excessive excretion of sialyloligosaccharides in urine is diagnostic of the disease. Affected mice progressively deteriorate as a consequence of severe organ dysfunction, especially of the kidney. The deficient phenotype can be corrected by transplanting null mutants with bone marrow from a transgenic line overexpressing human PPCA in erythroid precursor cells. The transgenic bone marrow gives a more efficient and complete correction of the visceral organs than normal bone marrow. Our data demonstrate the usefulness of this animal model, very similar to the human disease, for experimenting therapeutic strategies aimed to deliver the functional protein or gene to affected organs. Furthermore, they suggest the feasibility of gene therapy for galactosialidosis and other disorders, using bone marrow cells engineered to overexpress and secrete the correcting lysosomal protein.
DOI：
10.1016/s0021-9258(19)50665-2
发表时间：
1992-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
H. Jackman;P. Morris;P. Deddish;R. Skidgel;E. G. Erdös
通讯作者：
H. Jackman;P. Morris;P. Deddish;R. Skidgel;E. G. Erdös
骨髓移植可纠正溶酶体贮积症中枢神经系统神经元的酶缺陷。
DOI：
10.1073/pnas.91.8.2970
发表时间：
1994
影响因子：
11.1
作者：
Walkley,SU;Thrall,MA;Dobrenis,K;Huang,M;March,PA;Siegel,DA;Wurzelmann,S
通讯作者：
Wurzelmann,S
影响因子：
4.8
作者：
Krivit,W;Shapiro,E;Hoogerbrugge,PM;Moser,HW
通讯作者：
Moser,HW