title: Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: implications for assessment of therapeutic interventions in hurler syndrome.
abstract: Hurler syndrome (mucopolysaccharidosis type I [MPS I]) is a uniformly lethal autosomal recessive storage disease caused by absence of the enzyme alpha-l-iduronidase (IDUA), which is involved in lysosomal degradation of sulfated glycosaminoglycans (GAGs). Cardiomyopathy and valvar insufficiency occur as GAGs accumulate in the myocardium, spongiosa of cardiac valves, and myointima of coronary arteries. Here we report the functional, biochemical, and morphologic cardiac findings in the MPS I mouse. We compare the cardiac functional and histopathological findings in the mouse to human MPS I. In MPS I mice, we have noted aortic insufficiency, increased left ventricular size, and decreased ventricular function. Aortic and mitral valves are thickened and the aortic root is dilated. However, murine MPS I is not identical to human MPS I. Myointimal proliferation of epicardial coronary arteries is unique to human MPS I, whereas dilation of aortic root appears unique to murine MPS I. Despite the differences between murine and human MPS I, the murine model provides reliable in vivo outcome parameters, such as thickened and insufficient aortic valves and depressed cardiac function that can be followed to assess the impact of therapeutic interventions in preclinical studies in Hurler syndrome.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA. braun002@umn.edu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Braunlin
authors.forename: Shannon
authors.initials: S
authors.lastname: Mackey-Bojack
authors.forename: Angela
authors.initials: A
authors.lastname: Panoskaltsis-Mortari
authors.forename: James M
authors.initials: JM
authors.lastname: Berry
authors.forename: Ron T
authors.initials: RT
authors.lastname: McElmurry
authors.forename: Megan
authors.initials: M
authors.lastname: Riddle
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Sun
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Clarke
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000473:pathology; D004549:Elastin / Q000032:analysis; D006025:Glycosaminoglycans / Q000032:analysis / Q000378:metabolism; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D006351:Heart Valves / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008059:Mucopolysaccharidosis I / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D010496:Pericardium / Q000473:pathology; D014463:Ultrasonography
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; C013786:A73025; D004549:Elastin