Accumulation of abnormal amounts of glycosaminoglycans in murine mucopolysaccharidosis type VII neural progenitor cells does not alter the growth rate or efficiency of differentiation into neurons

被引:14
作者
Heuer, GG
Skorupa, AF
Alur, RKP
Jiang, KL
Wolfe, JH
机构
[1] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA
[2] Univ Penn, Sch Vet Med, Ctr Comparat Med Genet, Philadelphia, PA 19104 USA
[3] Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Div Neurol, Philadelphia, PA 19104 USA
关键词
D O I
10.1006/mcne.2000.0917
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mucopolysaccharidosis type VII (MPS VII) results from deficiencies in the gene encoding the lysosomal enzyme beta -glucuronidase (GUSB). To study how the genetic and biochemical defects of MPS disease affect neural cell populations, neural progenitor cells (NPCs) were isolated from MPS VII mice and normal littermates. After growth in culture, approximately 90% of cells from both genotypes were nestin positive, a marker for NPCs, and lacked markers associated with lineage commitment. The mutant NPCs contained elevated levels of undegraded glycosaminoglycans (GAGs), the substrate for GUSB. Transduction with a retrovirus-vector expressing normal GUSB resulted in correction of the biochemical defects. Because of the demonstrated roles that GAGs and proteoglycans have in NPC biology and neural development, we tested whether the alterations in GAG metabolism affected MPS VII NPC properties regulated by GAG-containing molecules. MPS VII NPC cultures had growth rates in response to FGF-2 that were similar to normal cultures and the efficiency of differentiation into neurons was the same as with normal cells. Thus, even though isolated NPCs accumulate abnormally high levels of GAGs, these two key developmental properties were not altered when the cells were examined outside the milieu of the diseased brain.
引用
收藏
页码:167 / 178
页数:12
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