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Cited by 100Down syndrome and intellectual disability researchAlzheimer's disease research and treatmentsGenetics and Neurodevelopmental Disorders

Normalizing the gene dosage of Dyrk1A in a mouse model of down syndrome rescues several Alzheimer’s disease phenotypes

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García-Cerro, Susana, Rueda, Noemí, Vidal, Verónica, Lantigua, Sara, Martínez-Cué, Carmen·2017·Neurobiology of Disease
DOI 10.1016/j.nbd.2017.06.010
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Abstract

The intellectual disability that characterizes Down syndrome (DS) is primarily caused by prenatal changes in central nervous system growth and differentiation. However, in later life stages, the cognitive abilities of DS individuals progressively decline due to accelerated aging and the development of Alzheimer's disease (AD) neuropathology. The AD neuropathology in DS has been related to the overexpression of several genes encoded by Hsa21 including DYRK1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which encodes a protein kinase that performs crucial functions in the regulation of multiple signaling pathways that contribute to normal brain development and adult brain physiology. Studies performed in vitro and in vivo in animal models overexpressing this gene have demonstrated that the DYRK1A gene also plays a crucial role in several neurodegenerative processes found in DS. The Ts65Dn (TS) mouse bears a partial triplication of several Hsa21 orthologous genes, including Dyrk1A, and replicates many DS-like abnormalities, including age-dependent cognitive decline, cholinergic neuron degeneration, increased levels of APP and Aβ, and tau hyperphosphorylation. To use a more direct approach to evaluate the role of the gene dosage of Dyrk1A on the neurodegenerative profile of this model, TS mice were crossed with Dyrk1A KO mice to obtain mice with a triplication of a segment of Mmu16 that includes this gene, mice that are trisomic for the same genes but only…

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  • Subtracting one copy of Dyrk1a at conception from otherwise trisomic mice improved cognitive, neurological and Alzheimer disease-like phenotypes.

    “Subtracting one copy of Dyrk1a at conception from otherwise trisomic mice improved cognitive, neurological and Alzheimer disease-like phenotypes (Garcia-Cerro et al., 2014; Garcia-Cerro et al., 2017) and improved T-maze and contextual fear conditioning tests (Jiang et al., 2015).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Garcia-Cerro et al., 2017

  • Ts65Dn mice are one of many DS mouse models and have been the primary model used in DS preclinical neurobiological and neuro-behavioral research, including extensive use in testing therapies designed to normalize DS phenotypes.

    “Ts65Dn mice are one of many DS mouse models and have been the primary model used in DS preclinical neurobiological and neuro-behavioral research, including extensive use in testing therapies designed to normalize DS phenotypes (Garcia-Cerro et al., 2017; Gardiner, 2015; Reeves et al., 1995).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Garcia-Cerro et al., 2017

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Authors
García-Cerro, S., Rueda, N., Vidal, V., Lantigua, S., & Martínez-Cué, C.
Affiliations
  • Universitat de Barcelona (ES)
  • Universidad de Cantabria (ES)
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2017-10
Volume
106
Pages
76-88
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2017.06.010
OpenAlex
W2697000055
Cited by
100
References
9
Citations by year
2026: 9 · 2025: 7 · 2024: 11 · 2023: 8 · 2022: 18 · 2021: 21 · 2020: 10 · 2019: 8 · 2018: 7 · 2017: 1
FWCI
6.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • UCrea (University of Cantabria) (acceptedVersion, cc-by-nc-nd)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
Funders
  • Fundación Tatiana Pérez de Guzmán el Bueno
  • Fondation Jérôme Lejeune
  • Agencia Estatal de Investigación
  • Federación Española de Enfermedades Raras
  • European Commission
  • Ministerio de Economía y Competitividad (PSI-2016-76194-R)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
Down syndrome, Alzheimer's disease, DYRK1A, gene dosage, Ts65Dn mouse model, cholinergic neuron degeneration, amyloid-beta, tau hyperphosphorylation, senescent cells, cognitive decline, therapeutic target
MeSH terms
Dyrk Kinases, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Down Syndrome, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Nerve Degeneration, Peptide Fragments, Phenotype, Phosphorylation, Protein-Tyrosine Kinases, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, tau Proteins, Protein Serine-Threonine Kinases, Gene Dosage, Mice, 129 Strain, Cholinergic Neurons

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