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DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects
Open accessAbstract
Among the various phenotypes seen in Down syndrome (DS), mental retardation is the most common and most debilitating condition suffered by individuals with DS. The DYRK1A gene on human chromosome 21q22.2 encodes a subfamily of protein kinases that displays dual substrate specificities and is known to play a critical role in neurodevelopment. To study DS mental retardation, we have generated transgenic mice that contain only one copy of the complete human DYRK1A gene in a bacterial artificial chromosome. The transgenic mice showed significant impairment in hippocampal-dependent memory tasks in a Morris water maze. Interestingly, we observed shifts in both long-term potentiation and long-term depression, which suggests a role for DYRK1A in bidirectional synaptic plasticity. These mice represent the most clinically relevant DYRK1A mouse model to date and provide us a valuable tool for the in vivo study of mechanisms that underlie the learning and memory deficit in DS.
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“DYRK1A is a serine-threonine kinase that utilizes autophosphorylation to enhance activity and stabilize itself, regulates many downstream proteins and transcription factors, and has a crucial role during brain development (Ahn et al., 2006; Arron et al., 2006; Atas-Ozcan et al., 2021; Branchi et al., 2004; Canzonetta et al., 2008; Hammerle et al., 2011; Martinez de Lagran et al., 2004; Park and Ch”
From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Ahn et al., 2006
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Metadata
- Authors
- Ahn, K.-J., Jeong, H. K., Choi, H.-S., Ryoo, S.-R., Kim, Y. J., Goo, J.-S., Choi, S.-Y., Han, J.-S., Ha, I., & Song, W.-J.
- Affiliations
- Inje University (KR)
- Seoul National University (KR)
- Corresponding author
- Ha, Ilho
- Song, Woo-Joo
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 22
- Issue
- 3
- Pages
- 463-472
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2110646442
- Cited by
- 220
- References
- 54
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 11 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 17 · 2016: 9 · 2015: 6 · 2014: 15 · 2013: 15 · 2012: 27
- FWCI
- 14.00
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- DYRK1A, Down syndrome, intellectual disability, transgenic mouse model, bacterial artificial chromosome, synaptic plasticity, long-term potentiation, long-term depression, hippocampal-dependent memory, learning and memory impairment, protein kinases
- MeSH terms
- Dyrk Kinases, Animals, Disease Models, Animal, Down Syndrome, Humans, Immunohistochemistry, Learning Disabilities, Memory Disorders, Mice, Transgenic, Neuronal Plasticity, Protein-Tyrosine Kinases, Polymerase Chain Reaction, Protein Serine-Threonine Kinases, In Situ Hybridization, Fluorescence, Chromosomes, Artificial, Bacterial, Mice
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