Effects of individual segmental trisomies of human chromosome 21 syntenic regions on hippocampal long-term potentiation and cognitive behaviors in mice
Open accessAbstract
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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Dp16 mice exhibit hyperactive IFN signaling and recapitulate many phenotypes of DS including developmental delays, cranial malformations, and cognitive deficits.
“Notably, Dp16 mice exhibit hyperactive IFN signaling and recapitulate many phenotypes of DS including developmental delays, cranial malformations, and cognitive deficits.38,40,42,43,44,45”
From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [45]
The Discussion (page unavailable) reports that Dp(16)1Yey/+ mice have Down-syndrome-related cognitive phenotypes, including impaired learning and memory. This paper does not report hyperactive IFN signaling, developmental delays, or cranial malformations in these mice; searches for those terms found no supporting passage. (LLM, conf=0.87)
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“42–45 However, since murine App does not get processed or form pathological aggregates, Dp16 mice do not exhibit AD neuro-pathology, hence, we crossed Dp16 with the 5xFAD mouse model of AD to stimulate A β pathogenesis.”
- Authors
- Yu, T., Liu, C., Belichenko, P., Clapcote, S. J., Li, S., Pao, A., Kleschevnikov, A., Bechard, A. R., Asrar, S., Chen, R., Fan, N., Zhou, Z., Jia, Z., Chen, C., Roder, J. C., Liu, B., Baldini, A., Mobley, W. C., & Yu, Y. E.
- Affiliations
- Roswell Park Comprehensive Cancer Center (US)
- University of California San Diego (US)
- Mount Sinai Hospital (CA)
- Brigham and Women's Hospital (US)
- University of Toronto (CA)
- Louisiana State University Health Sciences Center New Orleans (US)
- New York Medical College (US)
- Baylor College of Medicine (US)
- Texas A&M University (US)
- Corresponding author
- Yu, Y. Eugene
- ORCID
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 1366
- Pages
- 162-171
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC3027718
- OpenAlex
- W1993684263
- Cited by
- 127
- References
- 5
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 13 · 2021: 15 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 14 · 2016: 12 · 2015: 6 · 2014: 6 · 2013: 5 · 2012: 10
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Roswell Park Alliance Foundation
- Louis Sklarow Memorial Fund
- Fondation Jerome Lejeune
- Children's Guild Foundation
- NIH (R01HL091519, R01NS066072, P30CA016056)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Down syndrome, mouse model, chromosome engineering, hippocampal long-term potentiation, learning and memory, intellectual disability, cognitive impairment
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Chromosomes, Human, Pair 21, Cognition Disorders, Conditioning, Classical, Disease Models, Animal, Down Syndrome, Electric Stimulation, Electroshock, Fear, Hippocampus, Humans, Mice, Inbred C57BL, Mice, Transgenic, Trisomy, Long-Term Potentiation, Patch-Clamp Techniques, Maze Learning, Mice, In Vitro Techniques
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