Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/81430
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Type: Journal article
Title: Neonatal bone marrow transplantation in MPS IIIA mice
Author: Lau, A.
Shamsani, N.
Winner, L.
Hassiotis, S.
King, B.
Hopwood, J.
Hemsley, K.
Citation: JIMD Reports, 2013; 8:121-132
Publisher: Springer
Issue Date: 2013
ISSN: 2192-8304
2192-8312
Statement of
Responsibility: 
Adeline A Lau, N. Jannah Shamsani, Leanne K. Winner, Sofia Hassiotis, Barbara M. King, John J. Hopwood, Kim M. Hemsley
Abstract: Patients with some neurological lysosomal storage disorders (LSD) exhibit improved clinical signs following bone marrow transplantation (BMT). The failure of mucopolysaccharidosis (MPS) type IIIA patients and adult mice with the condition to respond to this treatment may relate to factors such as impaired migration of donor-derived cells into the brain, insufficient enzyme production and/or secretion by the donor-derived microglial cells, or the age at which treatment is initiated. To explore these possibilities, we treated neonatal MPS IIIA mice with whole unfractionated bone marrow and observed that nucleated blood cell reconstitution occurred to a similar degree in MPS IIIA mice receiving green fluorescent protein (GFP)-expressing normal (treatment group) or MPS IIIA-GFP marrow (control group) and normal mice receiving normal-GFP marrow (control group). Further, similar distribution patterns of GFP+ normal or MPS IIIA donor–derived cells were observed throughout the MPS IIIA mouse brain. We demonstrate that N-sulfoglucosamine sulfohydrolase (SGSH), the enzyme deficient in MPS IIIA, is produced and secreted in a manner proportional to that of other lysosomal enzymes. However, despite this, overall brain SGSH activity was unchanged in MPS IIIA mice treated with normal marrow and the lysosomal storage burden in whole brain homogenates did not decrease, most likely due to donor-derived cells comprising <0.24% of total recipient brain cells in all groups. This suggests that the failure of MPS IIIA patients and mice to respond to BMT may occur as a result of insufficient donor-derived enzyme production and/or uptake by host brain cells.
Rights: © SSIEM and Springer-Verlag Berlin Heidelberg 2013
RMID: 0020132399
DOI: 10.1007/8904_2012_169
Appears in Collections:Paediatrics publications

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