Mammalian Genome

, Volume 21, Issue 5–6, pp 258–267 | Cite as

Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice

  • Tao Yu
  • Steven J. Clapcote
  • Zhongyou Li
  • Chunhong Liu
  • Annie Pao
  • Allison R. Bechard
  • Sandra Carattini-Rivera
  • Sei-Ichi Matsui
  • John C. Roder
  • Antonio Baldini
  • William C. Mobley
  • Allan Bradley
  • Y. Eugene YuEmail author


Copy-number variation in the human genome can be disease-causing or phenotypically neutral. This type of genetic rearrangement associated with human chromosome 21 (Hsa21) underlies partial Monosomy 21 and Trisomy 21. Mental retardation is a major clinical manifestation of partial Monosomy 21. To model this human chromosomal deletion disorder, we have generated novel mouse mutants carrying heterozygous deletions of the 2.3- and 1.1-Mb segments on mouse chromosome 10 (Mmu10) and Mmu17, respectively, which are orthologous to the regions on human 21q22.3, using Cre/loxP-mediated chromosome engineering. Alterations of the transcriptional levels of genes within the deleted intervals reflect gene-dosage effects in the mutant mice. The analysis of cognitive behaviors shows that the mutant mice carrying the deletion on either Mmu10 or Mmu17 are impaired in learning and memory. Therefore, these mutants represent mouse models for Monosomy 21-associated mental retardation, which can serve as a powerful tool to study the molecular mechanism underlying the clinical phenotype and should facilitate efforts to identify the haploinsufficient causative genes.


Morris Water Maze Syntenic Region Morris Water Maze Test Heterozygous Deletion Partial Monosomy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank Paul Szurek and Jeffrey LaDuca for their assistance. This project was supported in part by grants to Y. E. Yu from the Louis Sklarow Memorial Fund, the Jerome Lejeune Foundation, and the NIH (R0HL091519).

Supplementary material

335_2010_9262_MOESM1_ESM.doc (112 kb)
Supplementary material 1 (DOC 111 kb)


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Tao Yu
    • 1
  • Steven J. Clapcote
    • 2
  • Zhongyou Li
    • 1
  • Chunhong Liu
    • 1
  • Annie Pao
    • 1
  • Allison R. Bechard
    • 3
  • Sandra Carattini-Rivera
    • 4
  • Sei-Ichi Matsui
    • 1
  • John C. Roder
    • 3
  • Antonio Baldini
    • 5
  • William C. Mobley
    • 6
  • Allan Bradley
    • 7
  • Y. Eugene Yu
    • 1
    Email author
  1. 1.Genetics Program and Department of Cancer GeneticsRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Institute of Membrane and Systems BiologyUniversity of LeedsLeedsUK
  3. 3.Samuel Lunenfeld Research InstituteMount Sinai Hospital, University of TorontoTorontoCanada
  4. 4.Department of Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  5. 5.Institute of Biosciences and TechnologyTexas A&M University Health Science CenterHoustonUSA
  6. 6.Department of NeurosciencesUniversity of California at San Diego, School of MedicineLa JollaUSA
  7. 7.Wellcome Trust Sanger InstituteWellcome Trust Genome CampusCambridgeUK

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