title: A mouse model of Down syndrome trisomic for all human chromosome 21 syntenic regions.
abstract: Down syndrome (DS) is caused by the presence of an extra copy of human chromosome 21 (Hsa21) and is the most common genetic cause for developmental cognitive disability. The regions on Hsa21 are syntenically conserved with three regions located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. In this report, we describe a new mouse model for DS that carries duplications spanning the entire Hsa21 syntenic regions on all three mouse chromosomes. This mouse mutant exhibits DS-related neurological defects, including impaired cognitive behaviors, reduced hippocampal long-term potentiation and hydrocephalus. These results suggest that when all the mouse orthologs of the Hsa21 genes are triplicated, an abnormal cognitively relevant phenotype is the final outcome of the elevated expressions of these orthologs as well as all the possible functional interactions among themselves and/or with other mouse genes. Because of its desirable genotype and phenotype, this mutant may have the potential to serve as one of the reference models for further understanding the developmental cognitive disability associated with DS and may also be used for developing novel therapeutic interventions for this clinical manifestation of the disorder.
authors.affiliation: Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Zhongyou
authors.initials: Z
authors.lastname: Li
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Jia
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liu
authors.forename: Shaomin
authors.initials: S
authors.lastname: Li
authors.forename: Suhail
authors.initials: S
authors.lastname: Asrar
authors.forename: Annie
authors.initials: A
authors.lastname: Pao
authors.forename: Rongqing
authors.initials: R
authors.lastname: Chen
authors.forename: Ni
authors.initials: N
authors.lastname: Fan
authors.forename: Sandra
authors.initials: S
authors.lastname: Carattini-Rivera
authors.forename: Allison R
authors.initials: AR
authors.lastname: Bechard
authors.forename: Shoshana
authors.initials: S
authors.lastname: Spring
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
authors.forename: George
authors.initials: G
authors.lastname: Stoica
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Matsui
authors.forename: Norma J
authors.initials: NJ
authors.lastname: Nowak
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.forename: Allan
authors.initials: A
authors.lastname: Bradley
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Yu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D018737:Hand Strength / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D010805:Physical Conditioning, Animal; D011247:Pregnancy; D026801:Synteny / Q000235:genetics