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

Mucopolysaccharidosis type VII (MPS VII) results from deficiencies in the g ene encoding the lysosomal enzyme beta -glucuronidase (GUSB). To study how the genetic and biochemical defects of MPS disease affect neural cell popul ations, neural progenitor cells (NPCs) were isolated from MPS VII mice and normal littermates. After growth in culture, approximately 90% of cells fro m both genotypes were nestin positive, a marker for NPCs, and lacked marker s associated with lineage commitment. The mutant NPCs contained elevated le vels of undegraded glycosaminoglycans (GAGs), the substrate for GUSB. Trans duction with a retrovirus-vector expressing normal GUSB resulted in correct ion of the biochemical defects. Because of the demonstrated roles that GAGs and proteoglycans have in NPC biology and neural development, we tested wh ether the alterations in GAG metabolism affected MPS VII NPC properties reg ulated by GAG-containing molecules. MPS VII NPC cultures had growth rates i n 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, e ven though isolated NPCs accumulate abnormally high levels of GAGs, these t wo key developmental properties were not altered when the cells were examin ed outside the milieu of the diseased brain.