TY - JOUR
T1 - Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice
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
N1 - Funding Information:
This project was supported in part by grants from the Roswell Park Alliance Foundation , the Louis Sklarow Memorial Fund , the Fondation Jerome Lejeune , the Children's Guild Foundation , and the NIH ( R01HL091519 and R01NS066072 ) and by the Cancer Center Support Grant from the NIH ( P30CA016056 ).
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - cognitive deficits
KW - down syndrome
KW - long-term potentiation
KW - mouse models
KW - trisomy 21
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U2 - 10.1016/j.brainres.2010.09.107
DO - 10.1016/j.brainres.2010.09.107
M3 - Article
C2 - 20932954
AN - SCOPUS:79251627273
SN - 0006-8993
VL - 1366
SP - 162
EP - 171
JO - Brain Research
JF - Brain Research
ER -