Document Detail


Trans-generational exposure to low levels of rhodamine B does not adversely affect litter size or liver function in murine mucopolysaccharidosis type IIIA.
MedLine Citation:
PMID:  20650670     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MPS IIIA is a lysosomal storage disorder caused by mutations in the sulphamidase gene, resulting in the accumulation of heparan sulphate glycosaminoglycans (HS GAGs). Symptoms predominantly manifest in the CNS and there is no current therapy that effectively addresses neuropathology in MPS IIIA patients. Recent studies in MPS IIIA mice have shown that rhodamine B substrate deprivation therapy (SDT) (also termed substrate reduction therapy/SRT) inhibits GAG biosynthesis and, improves both somatic and CNS disease pathology. Acute overexposure to high doses of rhodamine B results in liver toxicity and is detrimental to reproductive ability. However, the long-term effects of decreasing GAG synthesis, at the low dose sufficient to alter neurological function are unknown. A trans-generational study was therefore initiated to evaluate the continuous exposure of rhodamine B treatment in MPS IIIA mice over 4 generations, including treatment during pregnancy. No alterations in litter size, liver histology or liver function were observed. Overall, there are no long-term issues with the administration of rhodamine B at the low dose tested and no adverse effects were noted during pregnancy in mice.
Authors:
Ainslie L K Roberts; Janice M Fletcher; Lynette Moore; Sharon Byers
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-22
Journal Detail:
Title:  Molecular genetics and metabolism     Volume:  101     ISSN:  1096-7206     ISO Abbreviation:  Mol. Genet. Metab.     Publication Date:    2010 Oct-Nov
Date Detail:
Created Date:  2010-10-05     Completed Date:  2011-01-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805456     Medline TA:  Mol Genet Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  208-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Genetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, Australia. ainslie.derrickroberts@adelaide.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Female
Glycosaminoglycans / antagonists & inhibitors*,  biosynthesis
Litter Size / drug effects
Liver / drug effects*,  pathology,  physiology
Mice
Mucopolysaccharidosis III / genetics,  physiopathology*
Pregnancy
Rhodamines / therapeutic use*
Chemical
Reg. No./Substance:
0/Glycosaminoglycans; 0/Rhodamines; 14899-08-2/rhodamine B

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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