Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice

Arylsulfatase G inactivation causes loss of heparan sulfate 3- O -sulfatase activity and mucopolysaccharidosis in mice

“…Patients lacking these enzymes have MPS type III disorders, which are subclassified as Sanfilippo diseases on the basis of their storage of heparan sulfate with a modified or unmodified glucosamine residue at the NRE as well as their pathological presentation (6). ARSG also acts on a terminal glucosamine residue, and its deficiency results in the storage of heparan sulfate, causing neuropathology and behavioral defects characteristic of other Sanfilippo disease models (18,(22)(23)(24)(25). Thus, we propose that ARSG deficiency defines a fifth type of Sanfilippo disease, which we propose be termed MPS IIIE.…”

Whole body correction of mucopolysaccharidosis IIIA by intracerebrospinal fluid gene therapy

“…We and others have determined that by 2 months of age, MPS IIIA mice have established pathology in brain and somatic organs, with significant accumulation of GAGs and lysosomal distention (7,33). In MPS IIIA mice 6 to 18 weeks of age, repeated intra-CSF ERT achieved partial, but not complete, reversion of the disease phe- tive of full phenotypic reversal, while untreated MPS IIIA mice showed behavioral deficits as soon as 10 weeks of age (67).…”

Lessons learnt from animal models: pathophysiology of neuropathic lysosomal storage disorders

“…This potentially indicates the presence of modifier genes in the mixed genetic background, a hypothesis put forward to explain the difference in symptoms in CLN3 knock-out mice, when mixed-strain and C57BL/6J backgrounds were compared (Katz and Johnson 2001). Interestingly, hypoactivity in the open field was observed in both MPS IIIA strains when naïvely tested mice were used (Hemsley and Hopwood 2005;Lau et al 2008;Hemsley et al 2009b), as were other behavioral abnormalities (e.g., memory and learning deficits; Gliddon and Hopwood 2004;Crawley et al 2006;Hemsley et al 2009b). Consideration therefore needs to be given to the contribution that genetic background makes to the clinical phenotype of animal models of LSD, and where possible, phenotyping should be carried out on several different genetic backgrounds to explore the robustness of the disease-related phenotype.…”

“…In contrast, MPS IIIA mice (Bhaumik et al 1999;Bhattacharyya et al 2001;Crawley et al 2006) exhibit significant and early-disease-stage cognitive impairment, with deficits in open-field activity (exploration; Hemsley and Hopwood 2005;Lau et al 2008), elevated-plus maze activity (anxiety; Lau et al 2008), and performance of the Morris water maze test (memory and learning; Gliddon and Hopwood 2004;Fraldi et al 2007;Hemsley et al 2009b) reported. Motor changes are also observed, including gaitwidth abnormalities (Hemsley and Hopwood 2005;Crawley et al 2006) and swim speed (Hemsley et al unpublished data), albeit at later stages in the disease process.…”