muscleblind1, but not dmpk or six5, contributes to a complex phenotype of muscular and motivational deficits in mouse models of myotonic dystrophymuscleblind1,但不是dmpk或six5,导致一个复杂表型的肌肉和肌强直性营养不良动机赤字在小鼠模型.pdfVIP

Muscleblind1, but Not Dmpk or Six5, Contributes to a Complex Phenotype of Muscular and Motivational Deficits in Mouse Models of Myotonic Dystrophy 1 2 2 2 1 2 Anna Matynia , Carina Hoi Ng , Warunee Dansithong , Andy Chiang , Alcino J. Silva , Sita Reddy * 1 Departments of Neurobiology, Psychiatry Biobehavioral Sciences, Psychology and the Brain Research Institute, Gonda Neuroscience and Genetics Center, University of California Los Angeles, Los Angeles, California, United States of America, 2 Institute for Genetic Medicine, University of Southern California, Los Angeles, California, United States of America Abstract Assessment of molecular defects that underlie cognitive deficits observed in mendelian disorders provides a unique opportunity to identify key regulators of human cognition. Congenital Myotonic Dystrophy 1 (cDM1), a multi-system disorder is characterized by both cognitive deficits and a spectrum of behavioral abnormalities, which include visuo-spatial memory deficits, anxiety and apathy. Decreased levels of DMPK (Dystrophia Myotonica-protein kinase), SIX5, a transcription factor or MBNL1 (Muscleblind-like 1), an RNA splice regulator have been demonstrated to contribute to distinct features of cDM1. Mouse strains in which either Dmpk, Six5 or Mbnl1 are inactivated were therefore studied to determine the relative contribution of each gene to these cognitive functions. The open field and elevated plus maze tasks were used to examine anxiety, sucrose consumption was used to assess motivation, whereas the water maze and context fear conditioning were used to examine spatial learning and memory. Cognitive and behavioral abnormalities were observed only in Mbnl1 deficient mice, which demonstrate be