title: Mouse model of Sanfilippo syndrome type B: relation of phenotypic features to background strain.
abstract: Sanfilippo syndrome type B or mucopolysaccharidosis type III B (MPS IIIB) is a lysosomal storage disorder that is inherited in autosomal recessive manner. It is characterized by systemic heparan sulfate accumulation in lysosomes due to deficiency of the enzyme alpha-N-acetylglucosaminidase (Naglu). Devastating clinical abnormalities with severe central nervous system involvement and somatic disease lead to premature death. A mouse model of Sanfilippo syndrome type B was created by targeted disruption of the gene encoding Naglu, providing a powerful tool for understanding pathogenesis and developing novel therapeutic strategies. However, the JAX GEMM Strain B6.129S6-Naglutm1Efn mouse, although showing biochemical similarities to humans with Sanfilippo syndrome, exhibits aging and behavioral differences. We observed idiosyncrasies, such as skeletal dysmorphism, hydrocephalus, ocular abnormalities, organomegaly, growth retardation, and anomalies of the integument, in our breeding colony of Naglu mutant mice and determined that several of them were at least partially related to the background strain C57BL/6. These background strain abnormalities, therefore, potentially mimic or overlap signs of the induced syndrome in our mice. Our observations may prove useful in studies of Naglu mutant mice. The necessity for distinguishing background anomalies from signs of the modeled disease is apparent.
authors.affiliation: Department of Pathology, Division of Comparative Medicine, University of South Florida, College of Medicine, 12901 Bruce B. Downs Blvd., MDC 78, Tampa, Florida, 33612, USA.
authors.forename: Sylvia I
authors.initials: SI
authors.lastname: Gografe
authors.forename: Svitlana
authors.initials: S
authors.lastname: Garbuzova-Davis
authors.forename: Alison E
authors.initials: AE
authors.lastname: Willing
authors.forename: Ken
authors.initials: K
authors.lastname: Haas
authors.forename: Wilfredo
authors.initials: W
authors.lastname: Chamizo
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000118:Acetylglucosaminidase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000013:Congenital Abnormalities / Q000235:genetics / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000002:abnormalities / Q000235:genetics* / Q000378:metabolism; D018345:Mice, Knockout; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D012098:Reproduction / Q000235:genetics
chemical_list: C033079:alpha-N-acetyl-D-glucosaminidase; D000118:Acetylglucosaminidase