title: Cardiac and ocular pathologies in a mouse model of mucopolysaccharidosis type VI.
abstract: Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease caused by a deficiency of arylsulfatase B (ASB) which has its function in the sequential degradation of glycosaminoglycans (GAG). Targeted disruption of the ASB gene resulted in a mouse model of MPS VI that has been closely investigated for skeletal and chondral dysplasia. As ocular and cardiac impairment are also clinically important manifestations of the MPS VI syndrome, the present study was initiated for detailed biochemical, histologic and functional analysis of cornea, optic nerve and heart in ASB-deficient mice. Biochemical evidence for GAG-storage could be obtained for liver, kidney, spleen and myocardium as well as for heart valves, cornea and optic nerve from ASB-deficient mice. In MPS VI mice, histology revealed structural impairment of corneal stroma and epithelium as well as a thickening of the heart valves. According to histologic investigations, the optic nerve appeared not to be altered. However, GAG-storage in the dura mater could be demonstrated in MPS VI mice. Heart function was assessed by echocardiography. While the dimensions of MPS VI hearts were not altered, these hearts clearly showed decreased myocardial contraction and a 50% reduction of cardiac output. In addition, insufficiencies in the mitral and aortic valves were detected. Thus, ASB-deficient mice resemble the phenotype of human MPS VI not only in the skeletal but also in the ocular and cardiac symptoms. To our knowledge, these in vivo evaluations of heart function represent the first respective investigation of a MPS VI animal model and should provide a valuable measure for therapy studies in the MPS VI mouse.
authors.affiliation: Institut für Molekulare Medizin und Zellforschung, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Oliver F
authors.initials: OF
authors.lastname: Strauch
authors.forename: Jörg
authors.initials: J
authors.lastname: Stypmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinheckel
authors.forename: Elke
authors.initials: E
authors.lastname: Martinez
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Haverkamp
authors.forename: Christoph
authors.initials: C
authors.lastname: Peters
mesh_terms: D000818:Animals; D003315:Cornea / Q000473:pathology*; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology*; D006351:Heart Valves / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009087:Mucopolysaccharidosis VI / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics / Q000378:metabolism*; D009900:Optic Nerve / Q000473:pathology*
chemical_list: D006025:Glycosaminoglycans; D020051:N-Acetylgalactosamine-4-Sulfatase