title: Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice.
abstract: Neuraminidase initiates the hydrolysis of sialo-glycoconjugates by removing their terminal sialic acid residues. In humans, primary or secondary deficiency of this enzyme leads to two clinically similar neurodegenerative lysosomal storage disorders: sialidosis and galactosialidosis (GS). Mice nullizygous at the Neu1 locus develop clinical abnormalities reminiscent of early-onset sialidosis in children, including severe nephropathy, progressive edema, splenomegaly, kyphosis and urinary excretion of sialylated oligosaccharides. Although the sialidosis mouse model shares clinical and histopathological features with GS mice and GS patients, we have identified phenotypic abnormalities that seem specific for sialidosis mice. These include progressive deformity of the spine, high incidence of premature death, age-related extramedullary hematopoiesis, and lack of early degeneration of cerebellar Purkinje cells. The differences and similarities identified in these sialidosis and GS mice may help to better understand the pathophysiology of these diseases in children and to identify more targeted therapies for each of these diseases.
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: de Geest
authors.forename: Erik
authors.initials: E
authors.lastname: Bonten
authors.forename: Linda
authors.initials: L
authors.lastname: Mann
authors.forename: Jean
authors.initials: J
authors.lastname: de Sousa-Hitzler
authors.forename: Christopher
authors.initials: C
authors.lastname: Hahn
authors.forename: Alessandra
authors.initials: A
authors.lastname: d'Azzo
mesh_terms: D000818:Animals; D002268:Carboxypeptidases / Q000378:metabolism*; D043402:Cathepsin A; D004195:Disease Models, Animal; D006411:Hematopoiesis, Extramedullary; D006801:Humans; D051379:Mice; D009081:Mucolipidoses / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D001616:beta-Galactosidase / Q000378:metabolism*
chemical_list: D009439:Neuraminidase; D001616:beta-Galactosidase; D002268:Carboxypeptidases; C468629:CTSA protein, human; D043402:Cathepsin A