title: Animal models for lysosomal storage disorders.
abstract: The lysosomal storage disorders (LSD) represent a heterogeneous group of inherited diseases characterized by the accumulation of non-metabolized macromolecules (by-products of cellular turnover) in different tissues and organs. LSDs primarily develop as a consequence of a deficiency in a lysosomal hydrolase or its co-factor. The majority of these enzymes are glycosidases and sulfatases, which in normal conditions participate in degradation of glycoconjugates: glycoproteins, glycosaminoproteoglycans, and glycolipids. Significant insights have been gained from studies of animal models, both in understanding mechanisms of disease and in establishing proof of therapeutic concept. These studies have led to the introduction of therapy for certain LSD subtypes, primarily by enzyme replacement or substrate reduction therapy. Animal models have been useful in elucidating molecular changes, particularly prior to onset of symptoms. On the other hand, it should be noted certain animal (mouse) models may have the underlying biochemical defect, but not show the course of disease observed in human patients. There is interest in examining therapeutic options in the larger spontaneous animal models that may more closely mimic the brain size and pathology of humans. This review will highlight lessons learned from studies of animal models of disease, drawing primarily from publications in 2011-2012.
authors.affiliation: Neurogenetics, Department of Neurology, New York University School of Medicine, New York, NY 10016, USA. Gregory.Pastores@nyumc.org
authors.forename: G M
authors.initials: GM
authors.lastname: Pastores
authors.forename: P A
authors.initials: PA
authors.lastname: Torres
authors.forename: B-J
authors.initials: BJ
authors.lastname: Zeng
mesh_terms: D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D000818:Animals; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D057057:Serine Proteases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D000091346:Tripeptidyl-Peptidase 1; D000520:alpha-Glucosidases / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D000091346:Tripeptidyl-Peptidase 1; D000520:alpha-Glucosidases; D057057:Serine Proteases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases