ABSTRACT
Several animal models have been developed for the mucopolysaccharidoses (MPSs), a group of lysosomal storage disorders caused by lysosomal hydrolase deficiencies that disrupt the catabolism of glycosaminoglycans (GAG). Among the MPS, the MPS-III (Sanfilippo) syndromes lacked an animal counterpart until recently. In this investigation of caprine MPS-IIID, the clinical, biochemical, morphological, and immunohistochemical studies revealed severe and mild phenotypes like those observed in human MPS III syndromes. Both forms of caprine MPS IIID result from a nonsense mutation and consequent deficiency of lysosomal N-acetylglucosamine 6-sulfatase (G6S) activity and are associated with tissue storage and urinary excretion of heparan sulfate (HS). Using special stains, immunohistochemistry, and electron microscopy, secondary lysosomes filled with GAG were identified in most tissues from affected goats. Primary neuronal accumulation of HS and the secondary storage of gangliosides were observed in the central nervous system (CNS) of these animals. In addition, morphological changes in the CNS such as neuritic expansions and other neuronal alterations that may have functional significance were also seen. The spectrum of lesions was greater in the severe form of caprine MPS IIID and included mild cartilaginous, bony, and corneal lesions. The more pronounced neurological deficits in the severe form were partly related to a greater extent of CNS dysmyelination. These findings demonstrate that caprine MPS IIID is a suitable animal model for the investigation of therapeutic strategies for MPS III syndromes.
Subject(s)
Brain/pathology , Gangliosides/analysis , Goat Diseases , Mucopolysaccharidosis III/pathology , Mucopolysaccharidosis III/veterinary , Spinal Cord/pathology , Animals , Animals, Newborn , Brain/ultrastructure , Cerebral Cortex/chemistry , Endothelium, Vascular/pathology , Endothelium, Vascular/ultrastructure , Female , Glycosaminoglycans/metabolism , Goats , Heparitin Sulfate/analysis , Heparitin Sulfate/metabolism , Humans , Immunohistochemistry , Liver/pathology , Liver/ultrastructure , Male , Mucopolysaccharidosis III/genetics , Muscle, Smooth, Vascular/pathology , Muscle, Smooth, Vascular/ultrastructure , Myocardium/pathology , Myocardium/ultrastructure , Neuraminidase/analysis , Neurons/pathology , Point Mutation , Renal Artery/pathology , Renal Artery/ultrastructure , Sulfatases/geneticsABSTRACT
The hatching of Heterodera glycines eggs in soybean root exudates collected after postemergence application of three herbicides, and the hatching potential of H. glycines eggs from females feeding on herbicide-treated plants, were measured in vitro. Hatching in all root exudate solutions (RES) was greater than in deionized water but less than in 0.003 M ZnSO solution. Filtering RES with a 0.22-mum-filter increased H. glycines hatching in RES. Application of acifluorfen, bentazon, and lactofen to foliage of soybean plants inhibited hatching of H. glycines eggs from the same plants. Hatching in RES from the different herbicide-treated soybeans was similar. Application of crop oil concentrate and non-ionic surfactant adjuvant to foliage did not affect hatching of H. glycines eggs from soybean plants.