title: Development of sensory, motor and behavioral deficits in the murine model of Sanfilippo syndrome type B.
abstract: BACKGROUND
  Mucopolysaccharidosis (MPS) IIIB (Sanfilippo Syndrome type B) is caused by a deficiency in the lysosomal enzyme N-acetyl-glucosaminidase (Naglu). Children with MPS IIIB develop disturbances of sleep, activity levels, coordination, vision, hearing, and mental functioning culminating in early death. The murine model of MPS IIIB demonstrates lysosomal distention in multiple tissues, a shortened life span, and behavioral changes.
  
  
  RESULTS
  To more thoroughly assess MPS IIIB in mice, alterations in circadian rhythm, activity level, motor function, vision, and hearing were tested. The suprachiasmatic nucleus (SCN) developed pathologic changes and locomotor analysis showed that MPS IIIB mice start their daily activity later and have a lower proportion of activity during the night than wild-type controls. Rotarod assessment of motor function revealed a progressive inability to coordinate movement in a rocking paradigm. Purkinje cell counts were significantly reduced in the MPS IIIB animals compared to age matched controls. By electroretinography (ERG), MPS IIIB mice had a progressive decrease in the amplitude of the dark-adapted b-wave response. Corresponding pathology revealed shortening of the outer segments, thinning of the outer nuclear layer, and inclusions in the retinal pigmented epithelium. Auditory-evoked brainstem responses (ABR) demonstrated progressive hearing deficits consistent with the observed loss of hair cells in the inner ear and histologic abnormalities in the middle ear.
  
  
  CONCLUSIONS
  The mouse model of MPS IIIB has several quantifiable phenotypic alterations and is similar to the human disease. These physiologic and histologic changes provide insights into the progression of this disease and will serve as important parameters when evaluating various therapies.
authors: Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America.
authors: Coy D
authors: CD
authors: Heldermon
authors: Anne K
authors: AK
authors: Hennig
authors: Kevin K
authors: KK
authors: Ohlemiller
authors: Judith M
authors: JM
authors: Ogilvie
authors: Erik D
authors: ED
authors: Herzog
authors: Annalisa
authors: A
authors: Breidenbach
authors: Carole
authors: C
authors: Vogler
authors: David F
authors: DF
authors: Wozniak
authors: Mark S
authors: MS
authors: Sands
mesh_terms: D000118:Acetylglucosaminidase / Q000172:deficiency; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology / Q000473:pathology; D002648:Child; D002940:Circadian Rhythm / Q000502:physiology; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000473:pathology; D004432:Ear, Middle / Q000473:pathology; D004596:Electroretinography; D005072:Evoked Potentials, Auditory / Q000502:physiology; D005260:Female; D006309:Hearing / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology*; D009084:Mucopolysaccharidosis III / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D010641:Phenotype; D012160:Retina / Q000473:pathology; D045442:Rotarod Performance Test; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000473:pathology; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: D000118:Acetylglucosaminidase
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