Transgenic Research

, Volume 23, Issue 2, pp 317–329 | Cite as

A novel mouse model for Down syndrome that harbor a single copy of human artificial chromosome (HAC) carrying a limited number of genes from human chromosome 21

  • Kenichi Miyamoto
  • Nobutaka Suzuki
  • Kosuke Sakai
  • Shuichi Asakawa
  • Tsuneko Okazaki
  • Jun Kudoh
  • Masashi Ikeno
  • Nobuyoshi Shimizu
Original Paper


Down syndrome (DS), also known as Trisomy 21, is the most common chromosome aneuploidy in live-born children and displays a complicated symptom. To date, several kinds of mouse models have been generated to understand the molecular pathology of DS, yet the gene dosage effects and gene(s)-phenotype(s) correlation are not well understood. In this study, we established a novel method to generate a partial trisomy mice using the mouse ES cells that harbor a single copy of human artificial chromosome (HAC), into which a small human DNA segment containing human chromosome 21 genes cloned in a bacterial artificial chromosome (BAC) was recombined. The produced mice were found to maintain the HAC carrying human genes as a mini-chromosome, hence termed as a Trans-Mini-Chromosomal (TMC) mouse, and HAC was transmitted for more than twenty generations independent from endogenous mouse chromosomes. The three human transgenes including cystathionine β-synthase, U2 auxiliary factor and crystalline alpha A were expressed in several mouse tissues with various expression levels relative to mouse endogenous genes. The novel system is applicable to any of human and/or mouse BAC clones. Thus, the TMC mouse carrying a HAC with a limited number of genes would provide a novel tool for studying gene dosage effects involved in the DS molecular pathogenesis and the gene(s)-phenotype(s) correlation.


Down syndrome Trans-mini-chromosomal mouse Human artificial chromosome Bacterial artificial chromosome Gene dosage effects 



Down syndrome


Human artificial chromosome


Bacterial artificial chromosome

TMC mouse

Trans-mini-chromosomal mouse


Cystathionine β-synthase


U2 auxiliary factor


Crystalline alpha A


Fluorescence in situ hybridization

ES cell

Embryonic stem cell


Quantitative polymerase chain reaction


Reverse transcription polymerase chain reaction



We thank Mr. Masahiko Maekawa (GSP laboratory Inc., Kawasaki, Japan) for the technical support of FISH. This work was supported by Grants-in-Aid for Scientific Research (B) (Grant Number 16390307), (A) (Grant Number 19209038), Young Scientists (B) (Grant Number 23791194) and Global COE program for Education and Research Centre for Human Metabolomic Systems Biology from the Ministry of Education, Culture, Sports, Science and Technology (MEXT).

Supplementary material

11248_2013_9772_MOESM1_ESM.pptx (238 kb)
Supplementary material 1 (PPTX 238 kb)


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Kenichi Miyamoto
    • 1
  • Nobutaka Suzuki
    • 2
  • Kosuke Sakai
    • 1
  • Shuichi Asakawa
    • 3
  • Tsuneko Okazaki
    • 2
  • Jun Kudoh
    • 1
  • Masashi Ikeno
    • 1
    • 2
  • Nobuyoshi Shimizu
    • 4
  1. 1.Laboratory of Gene MedicineKeio University School of MedicineTokyoJapan
  2. 2.Chromo Research Inc.NagoyaJapan
  3. 3.Laboratory of Aquatic Molecular Biology and Biotechnology, Graduate School of Agricultural and Life ScienceThe University of TokyoTokyoJapan
  4. 4.Advanced Research Center for Genome Super PowerKeio UniversityTsukubaJapan

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