title: Gastrointestinal pathology in a mouse model of mucopolysaccharidosis type IIIA.
abstract: Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder caused by a deficiency in sulphamidase (NS), a lysosomal enzyme required for the degradation of heparan sulphate glycosaminoglycans (gags). The MPS IIIA mouse is a naturally occurring model that accurately reflects the human pathology and disease course. It displays primarily central nervous system pathology accompanied by widespread accumulation of gag in somatic tissues. MPS IIIA mice exhibit greater bodyweight gain than normal littermates and attain a higher mature bodyweight. In this study, gastrointestinal morphology and function was characterised in the IIIA mouse. Stomach and duodenum weight increased in MPS IIIA mice and duodenum length also increased. An increased submucosal thickness was observed in MPS IIIA intestine compared to normal mice and lysosomal storage of gag was observed in this region. Storage was also observed in the lamina propria of the villus tip. All other morphometric measurements including villus height and crypt depth fell within the normal range. The gastric emptying half-life of solid and liquid meals decreased with age in normal mice whereas the T(1/2) of solid meals did not alter with age in MPS IIA mice such that they were elevated above normal by 38 weeks of age. Sucrase activity was higher than normal in MPS IIIA at all ages tested. These abnormalities in GI structure and function observed in MPS IIIA may contribute to weight gain in this disorder.
authors.affiliation: Department of Genetic Medicine, Matrix Biology Unit, Children, Youth and Women's Health Service, North Adelaide, SA, Australia.
authors.forename: Ainslie L K Derrick
authors.initials: AL
authors.lastname: Roberts
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Howarth
authors.forename: Wan Chin
authors.initials: WC
authors.lastname: Liaw
authors.forename: Simon
authors.initials: S
authors.lastname: Moretta
authors.forename: Stamatiki
authors.initials: S
authors.lastname: Kritas
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Lymn
authors.forename: Roger
authors.initials: R
authors.lastname: Yazbeck
authors.forename: Cuong
authors.initials: C
authors.lastname: Tran
authors.forename: Janice M
authors.initials: JM
authors.lastname: Fletcher
authors.forename: Ross N
authors.initials: RN
authors.lastname: Butler
authors.forename: Sharon
authors.initials: S
authors.lastname: Byers
mesh_terms: D000818:Animals; D001944:Breath Tests; D004195:Disease Models, Animal; D005746:Gastric Emptying / Q000502:physiology; D041981:Gastrointestinal Tract / Q000033:anatomy & histology / Q000473:pathology* / Q000502:physiology; D006801:Humans; D006867:Hydrolases / Q000172:deficiency; D051379:Mice; D009084:Mucopolysaccharidosis III / Q000473:pathology*; D009929:Organ Size; D013393:Sucrase / Q000378:metabolism
chemical_list: D006867:Hydrolases; C022708:N-sulfoglucosamine sulfohydrolase; D013393:Sucrase