title: Mouse-based genetic modeling and analysis of Down syndrome.
abstract: Down syndrome (DS), caused by human trisomy 21 (Ts21), can be considered as a prototypical model for understanding the effects of chromosomal aneuploidies in other diseases. Human chromosome 21 (Hsa21) is syntenically conserved with three regions in the mouse genome.
  
  
  
  A review of recent advances in genetic modeling and analysis of DS. Using Cre/loxP-mediated chromosome engineering, a substantial number of new mouse models of DS have recently been generated, which facilitates better understanding of disease mechanisms in DS.
  
  
  
  Based on evolutionary conservation, Ts21 can be modeled by engineered triplication of Hsa21 syntenic regions in mice. The validity of the models is supported by the exhibition of DS-related phenotypes.
  
  
  
  Although substantial progress has been made, it remains a challenge to unravel the relative importance of specific candidate genes and molecular mechanisms underlying the various clinical phenotypes.
  
  
  
  Further understanding of mechanisms based on data from mouse models, in parallel with human studies, may lead to novel therapies for clinical manifestations of Ts21 and insights to the roles of aneuploidies in other developmental disorders and cancers.
authors: The Children's Guild Foundation Down Syndrome Research Program, Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: Zhuo
authors: Z
authors: Xing
authors: The Children's Guild Foundation Down Syndrome Research Program, Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: Yichen
authors: Y
authors: Li
authors: The Children's Guild Foundation Down Syndrome Research Program, Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: Annie
authors: A
authors: Pao
authors: The Children's Guild Foundation Down Syndrome Research Program, Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: Abigail S
authors: AS
authors: Bennett
authors: Taub Institute for Research on Alzheimer's Disease and the Aging Brain and Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
authors: Benjamin
authors: B
authors: Tycko
authors: Department of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
authors: William C
authors: WC
authors: Mobley
authors: The Children's Guild Foundation Down Syndrome Research Program, Genetics Program and Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA yuejin.yu@roswellpark.org.|Cellular and Molecular Biology Program, Roswell Park Division of Graduate School, Genetics, Genomics and Bioinformatics Program, State University of New York at Buffalo, Buffalo, NY 14263, USA.
authors: Y Eugene
authors: YE
authors: Yu
mesh_terms: D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D002658:Developmental Disabilities; D004195:Disease Models, Animal; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005818:Genetic Engineering; D051379:Mice
keywords: Down syndrome; chromosome engineering; human trisomy 21; mouse models