Identification of molecules with altered expression in the brain of mouse model for down syndrome by comprehensive analyses

Abstract

Down syndrome (DS), caused by triplication of human chromosome 21, is the most common aneuploidy. A mouse model of DS may be useful for the investigation of DS pathophysiology. Ts1Cje mouse, an established DS mouse model, is widely used in DS research. It carries a trisomic segment of mouse chromosome 16 that contains a syntenic region to human chromosome 21. The brain of the Ts1Cje mouse has been analyzed morphologically and biochemically to elucidate DS pathophysiology. We have also demonstrated some abnormal phenotypes of this mouse model, such as enlarged brain ventricles, reduced embryonic and adult neurogenesis, and increased lipid peroxidation. Elucidating the underlying molecular mechanisms in the Ts1Cje mouse may improve understanding of the etiology of the phenotypic abnormalities of DS, including cognitive impairment and developmental retardation, and aid in development of therapeutic strategy. High-throughput gene and protein expression analyses, such as transcriptomics and proteomics, are useful for identification of molecules associated with the development of DS symptoms. In this review, alteration of molecular expression in the brain of a DS mouse model is highlighted, and possible molecular mechanisms underlying DS phenotypic abnormalities such as cognitive impairment and developmental retardation are discussed. © The Pharmaceutical Society of Japan.