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 Yu

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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 genedosage 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.

Original languageEnglish
Pages (from-to)258-267
Number of pages10
JournalMammalian Genome
Volume21
Issue number5-6
DOIs
Publication statusPublished - Jun 2010

Fingerprint

Chromosome Deletion
Intellectual Disability
Chromosome Disorders
Chromosomes, Human, Pair 21
Chromosomes, Human, Pair 10
Trisomy
Human Chromosomes
Human Genome
Down Syndrome
Genes
Chromosomes
Learning
Phenotype
Chromosome 21 monosomy

ASJC Scopus subject areas

  • Genetics
  • Medicine(all)

Cite this

Yu, T., Clapcote, S. J., Li, Z., Liu, C., Pao, A., Bechard, A. R., ... Yu, Y. E. (2010). Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice. Mammalian Genome, 21(5-6), 258-267. https://doi.org/10.1007/s00335-010-9262-x

Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice. / Yu, Tao; Clapcote, Steven J.; Li, Zhongyou; Liu, Chunhong; Pao, Annie; Bechard, Allison R.; Carattini-Rivera, Sandra; Matsui, Sei Ichi; Roder, John C.; Baldini, Antonio; Mobley, William C.; Bradley, Allan; Yu, Y. Eugene.

In: Mammalian Genome, Vol. 21, No. 5-6, 06.2010, p. 258-267.

Research output: Contribution to journalArticle

Yu, T, Clapcote, SJ, Li, Z, Liu, C, Pao, A, Bechard, AR, Carattini-Rivera, S, Matsui, SI, Roder, JC, Baldini, A, Mobley, WC, Bradley, A & Yu, YE 2010, 'Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice', Mammalian Genome, vol. 21, no. 5-6, pp. 258-267. https://doi.org/10.1007/s00335-010-9262-x
Yu, Tao ; Clapcote, Steven J. ; Li, Zhongyou ; Liu, Chunhong ; Pao, Annie ; Bechard, Allison R. ; Carattini-Rivera, Sandra ; Matsui, Sei Ichi ; Roder, John C. ; Baldini, Antonio ; Mobley, William C. ; Bradley, Allan ; Yu, Y. Eugene. / Deficiencies in the region syntenic to human 21q22.3 cause cognitive deficits in mice. In: Mammalian Genome. 2010 ; Vol. 21, No. 5-6. pp. 258-267.
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