title: Duplication of the entire 22.9 Mb human chromosome 21 syntenic region on mouse chromosome 16 causes cardiovascular and gastrointestinal abnormalities.
abstract: Down syndrome is caused by a genomic imbalance of human chromosome 21 which is mainly observed as trisomy 21. The regions on human chromosome 21 are syntenically conserved in three regions on mouse chromosomes 10, 16 and 17. Ts65Dn mice, the most widely used model for Down syndrome, are trisomic for approximately 56.5% of the human chromosome 21 syntenic region on mouse chromosome 16. To generate a more complete trisomic mouse model of Down syndrome, we have established a 22.9 Mb duplication spanning the entire human chromosome 21 syntenic region on mouse chromosome 16 in mice using Cre/loxP-mediated long-range chromosome engineering. The presence of the intact duplication in mice was confirmed by fluorescent in situ hybridization and BAC-based array comparative genomic hybridization. The expression levels of the genes within the duplication interval reflect gene-dosage effects in the mutant mice. The cardiovascular and gastrointestinal phenotypes of the mouse model were similar to those of patients with Down syndrome. This new mouse model represents a powerful tool to further understand the molecular and cellular mechanisms of Down syndrome.
authors.affiliation: Department of Cancer Genetics and Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Buffalo,NY 14263, USA.
authors.forename: Zhongyou
authors.initials: Z
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Masae
authors.initials: M
authors.lastname: Morishima
authors.forename: Annie
authors.initials: A
authors.lastname: Pao
authors.forename: Jeffrey
authors.initials: J
authors.lastname: LaDuca
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Conroy
authors.forename: Norma
authors.initials: N
authors.lastname: Nowak
authors.forename: Sei-Ichi
authors.initials: S
authors.lastname: Matsui
authors.forename: Isao
authors.initials: I
authors.lastname: Shiraishi
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Yu
mesh_terms: D000818:Animals; D018376:Cardiovascular Abnormalities / Q000235:genetics*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics*; D004065:Digestive System Abnormalities / Q000235:genetics*; D020440:Gene Duplication; D006801:Humans; D051379:Mice; D026801:Synteny; D014178:Translocation, Genetic