Trans-generational exposure to low levels of rhodamine B does not adversely affect litter size or liver function in murine mucopolysaccharidosis type IIIA |
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| Authors: | Ainslie L.K. Roberts Janice M. Fletcher Lynette Moore Sharon Byers |
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| Affiliation: | 1. Department of Genetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, Australia;2. Discipline of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia;3. Department of Surgical Pathology, SA Pathology, North Adelaide, SA 5006, Australia;4. Discipline of Genetics, University of Adelaide, SA, 2005, Australia;1. School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Key Laboratory of Chemistry and Engineering of Forest Products, Nanning, Guangxi 530008, China;2. School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, China;1. Institut für Chemie, Universität Potsdam, Karl-Liebknecht-Straße 24-25, D-14476 Potsdam, Federal Republic of Germany;2. Institut Lumière Matière, UMR5306 Université Claude Bernard Lyon 1-CNRS, Université de Lyon, 69622 Villeurbanne Cedex, France;3. Institut für Physik, Humboldt-Universität zu Berlin, Newtonstraße 15, D-12489 Berlin, Federal Republic of Germany;1. Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China;2. State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China;3. Suzhou Key Laboratory of Environment and Biosafety, Suzhou 215123, China;4. Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale University, 60 College Street, New Haven, CT 06520-8034, USA;1. Área de Química Analítica, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, San Luis, Argentina;2. Instituto de Química de San Luis (INQUISAL-CONICET), Chacabuco y Pedernera, 5700 San Luis, Argentina;3. Department of Chemistry, Wake Forest University, Winston-Salem, 2710, United States of America;1. Midwifery Master Study Programme, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia;2. Physiology Laboratory, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia;3. Division of Fertility, Endocrinology and Reproduction, Obstetric and Ginecology Laboratory, Saiful Anwar General Hospital, Faculty of Medicine, Brawijaya University, Malang, East Java, Indonesia |
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| Abstract: | 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. |
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