development of sensory, motor and behavioral deficits in the murine model of sanfilippo syndrome type b发展感觉、运动和行为赤字礼宾部主管综合征小鼠模型的b型.pdfVIP

Development of Sensory, Motor and Behavioral Deficits in the Murine Model of Sanfilippo Syndrome Type B 1 1 1 2 3 3 4 Coy D. Heldermon , Anne K. Hennig , Kevin K. Ohlemiller , Judith M. Ogilvie , Erik D. Herzog , Annalisa Breidenbach , Carole Vogler , David F. 5 1 Wozniak , Mark S. Sands * 1 Washington University in St. Louis, School of Medicine, St. Louis, Missouri, United States of America, 2 Saint Louis University, Department of Biology, St. Louis, Missouri, United States of America, 3 Washington University in St. Louis, Department of Biology, St. Louis, Missouri, United States of America, 4 Saint Louis University School of Medicine, St. Louis, Missouri, United States of America, 5 Washington University in St. Louis, Department of Psychiatry, St. Louis, Missouri, United States of America 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. Principal Findings. 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 inabil