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Mammalian Genome

, Volume 27, Issue 11–12, pp 538–555 | Cite as

Mouse models of Down syndrome: gene content and consequences

  • Meenal Gupta
  • A. Ranjitha Dhanasekaran
  • Katheleen J. GardinerEmail author
Article

Abstract

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), is challenging to model in mice. Not only is it a contiguous gene syndrome spanning 35 Mb of the long arm of Hsa21, but orthologs of Hsa21 genes map to segments of three mouse chromosomes, Mmu16, Mmu17, and Mmu10. The Ts65Dn was the first viable segmental trisomy mouse model for DS; it is a partial trisomy currently popular in preclinical evaluations of drugs for cognition in DS. Limitations of the Ts65Dn are as follows: (i) it is trisomic for 125 human protein-coding orthologs, but only 90 of these are Hsa21 orthologs and (ii) it lacks trisomy for ~75 Hsa21 orthologs. In recent years, several additional mouse models of DS have been generated, each trisomic for a different subset of Hsa21 genes or their orthologs. To best exploit these models and interpret the results obtained with them, prior to proposing clinical trials, an understanding of their trisomic gene content, relative to full trisomy 21, is necessary. Here we first review the functional information on Hsa21 protein-coding genes and the more recent annotation of a large number of functional RNA genes. We then discuss the conservation and genomic distribution of Hsa21 orthologs in the mouse genome and the distribution of mouse-specific genes. Lastly, we consider the strengths and weaknesses of mouse models of DS based on the number and nature of the Hsa21 orthologs that are, and are not, trisomic in each, and discuss their validity for use in preclinical evaluations of drug responses.

Keywords

Down Syndrome Morris Water Maze Context Fear Conditioning Preclinical Evaluation Partial Trisomy 
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.

Notes

Acknowledgments

This work was supported by the National Institute of Child Health and Human Development (HD071585) and the Linda Crnic Institute for Down Syndrome.

Supplementary material

335_2016_9661_MOESM1_ESM.xlsx (112 kb)
Supplementary material 1 (XLSX 112 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Meenal Gupta
    • 1
  • A. Ranjitha Dhanasekaran
    • 1
  • Katheleen J. Gardiner
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Pediatrics, Linda Crnic Institute for Down SyndromeUniversity of Colorado Denver School of MedicineAuroraUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Colorado Denver School of MedicineAuroraUSA
  3. 3.Human Medical Genetics and Genomics, and Neuroscience ProgramsUniversity of Colorado Denver School of MedicineAuroraUSA

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