Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice

Tao Yu, Chunhong Liu, Pavel Belichenko, Steven J. Clapcote, Shaomin Li, Annie Pao, Alexander Kleschevnikov, Allison R. Bechard, Suhail Asrar, Rongqing Chen, Ni Fan, Zhenyu Zhou, Zhengping Jia, Chu Chen, John C. Roder, Bin Liu, Antonio Baldini, William C. Mobley, Y. Eugene Yu

Research output: Contribution to journalArticle

Abstract

As the genomic basis for Down syndrome (DS), human trisomy 21 is the most common genetic cause of intellectual disability in children and young people. The genomic regions on human chromosome 21 (Hsa21) are syntenic to three regions in the mouse genome, located on mouse chromosome 10 (Mmu10), Mmu16, and Mmu17. Recently, we have developed three new mouse models using chromosome engineering carrying the genotypes of Dp(10)1Yey/+, Dp(16)1Yey/+, or Dp(17)1Yey/+, which harbor a duplication spanning the entire Hsa21 syntenic region on Mmu10, Mmu16, or Mmu17, respectively. In this study, we analyzed the hippocampal long-term potentiation (LTP) and cognitive behaviors of these models. Our results show that, while the genotype of Dp(17)1Yey/+ results in abnormal hippocampal LTP, the genotype of Dp(16)1Yey/+ leads to both abnormal hippocampal LTP and impaired learning/memory. Therefore, these mutant mice can serve as powerful tools for further understanding the mechanism underlying cognitively relevant phenotypes associated with DS, particularly the impacts of different syntenic regions on these phenotypes.

Original languageEnglish (US)
Pages (from-to)162-171
Number of pages10
JournalBrain Research
Volume1366
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Chromosomes, Human, Pair 21
Long-Term Potentiation
Trisomy
Human Chromosomes
Down Syndrome
Genotype
Phenotype
Chromosomes, Human, Pair 10
Intellectual Disability
Chromosomes
Learning
Genome

Keywords

  • cognitive deficits
  • down syndrome
  • long-term potentiation
  • mouse models
  • trisomy 21

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice. / Yu, Tao; Liu, Chunhong; Belichenko, Pavel; Clapcote, Steven J.; Li, Shaomin; Pao, Annie; Kleschevnikov, Alexander; Bechard, Allison R.; Asrar, Suhail; Chen, Rongqing; Fan, Ni; Zhou, Zhenyu; Jia, Zhengping; Chen, Chu; Roder, John C.; Liu, Bin; Baldini, Antonio; Mobley, William C.; Yu, Y. Eugene.

In: Brain Research, Vol. 1366, 2010, p. 162-171.

Research output: Contribution to journalArticle

Yu, T, Liu, C, Belichenko, P, Clapcote, SJ, Li, S, Pao, A, Kleschevnikov, A, Bechard, AR, Asrar, S, Chen, R, Fan, N, Zhou, Z, Jia, Z, Chen, C, Roder, JC, Liu, B, Baldini, A, Mobley, WC & Yu, YE 2010, 'Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice', Brain Research, vol. 1366, pp. 162-171. https://doi.org/10.1016/j.brainres.2010.09.107
Yu, Tao ; Liu, Chunhong ; Belichenko, Pavel ; Clapcote, Steven J. ; Li, Shaomin ; Pao, Annie ; Kleschevnikov, Alexander ; Bechard, Allison R. ; Asrar, Suhail ; Chen, Rongqing ; Fan, Ni ; Zhou, Zhenyu ; Jia, Zhengping ; Chen, Chu ; Roder, John C. ; Liu, Bin ; Baldini, Antonio ; Mobley, William C. ; Yu, Y. Eugene. / Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice. In: Brain Research. 2010 ; Vol. 1366. pp. 162-171.
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abstract = "As the genomic basis for Down syndrome (DS), human trisomy 21 is the most common genetic cause of intellectual disability in children and young people. The genomic regions on human chromosome 21 (Hsa21) are syntenic to three regions in the mouse genome, located on mouse chromosome 10 (Mmu10), Mmu16, and Mmu17. Recently, we have developed three new mouse models using chromosome engineering carrying the genotypes of Dp(10)1Yey/+, Dp(16)1Yey/+, or Dp(17)1Yey/+, which harbor a duplication spanning the entire Hsa21 syntenic region on Mmu10, Mmu16, or Mmu17, respectively. In this study, we analyzed the hippocampal long-term potentiation (LTP) and cognitive behaviors of these models. Our results show that, while the genotype of Dp(17)1Yey/+ results in abnormal hippocampal LTP, the genotype of Dp(16)1Yey/+ leads to both abnormal hippocampal LTP and impaired learning/memory. Therefore, these mutant mice can serve as powerful tools for further understanding the mechanism underlying cognitively relevant phenotypes associated with DS, particularly the impacts of different syntenic regions on these phenotypes.",
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AU - Yu, Tao

AU - Liu, Chunhong

AU - Belichenko, Pavel

AU - Clapcote, Steven J.

AU - Li, Shaomin

AU - Pao, Annie

AU - Kleschevnikov, Alexander

AU - Bechard, Allison R.

AU - Asrar, Suhail

AU - Chen, Rongqing

AU - Fan, Ni

AU - Zhou, Zhenyu

AU - Jia, Zhengping

AU - Chen, Chu

AU - Roder, John C.

AU - Liu, Bin

AU - Baldini, Antonio

AU - Mobley, William C.

AU - Yu, Y. Eugene

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