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 Kudo, Masashi Ikeno, Nobuyoshi Shimizu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)317-329
Number of pages13
JournalTransgenic Research
Volume23
Issue number2
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Human Artificial Chromosomes
Down syndrome
Chromosomes, Human, Pair 21
Human Chromosomes
Down Syndrome
animal models
chromosomes
mice
Genes
genes
gene dosage
trisomics
bacterial artificial chromosomes
Bacterial Artificial Chromosomes
Gene Dosage
Chromosomes
dose response
cystathionine
Cystathionine
phenotype

ASJC Scopus subject areas

  • Biotechnology
  • Genetics
  • Agronomy and Crop Science
  • Animal Science and Zoology

Cite this

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. / Miyamoto, Kenichi; Suzuki, Nobutaka; Sakai, Kosuke; Asakawa, Shuichi; Okazaki, Tsuneko; Kudo, Jun; Ikeno, Masashi; Shimizu, Nobuyoshi.

In: Transgenic Research, Vol. 23, No. 2, 2014, p. 317-329.

Research output: Contribution to journalArticle

Miyamoto, Kenichi ; Suzuki, Nobutaka ; Sakai, Kosuke ; Asakawa, Shuichi ; Okazaki, Tsuneko ; Kudo, Jun ; Ikeno, Masashi ; Shimizu, Nobuyoshi. / 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. In: Transgenic Research. 2014 ; Vol. 23, No. 2. pp. 317-329.
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