Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice

Vassiliki Fotaki, Mara Dierssen, Soledad Alcántara, Salvador Martínez, Eulàlia Martí, Caty Casas, Joana Visa, Eduardo Soriano, Xavier Estivill, Maria L. Arbonés

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Abstract

DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested. To gain insight into its physiological role, we have generated mice deficient in DyrklA function by gene targeting. Dyrk1A-/- null mutants presented a general growth delay and died during midgestation. Mice heterozygous for the mutation (Dyrk1A+/-) showed decreased neonatal viability and a significant body size reduction from birth to adulthood. General neurobehavioral analysis revealed preweaning developmental delay of Dyrk1A+/- mice and specific alterations in adults. Brains of Dyrk1A+/- mice were decreased in size in a region-specific manner, although the cytoarchitecture and neuronal components in most areas were not altered. Cell counts showed increased neuronal densities in some brain regions and a specific decrease in the number of neurons in the superior colliculus, which exhibited a significant size reduction. These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies.

Original languageEnglish
Pages (from-to)6636-6647
Number of pages12
JournalMolecular and Cellular Biology
Volume22
Issue number18
DOIs
Publication statusPublished - 1 Sep 2002

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Fotaki, V., Dierssen, M., Alcántara, S., Martínez, S., Martí, E., Casas, C., Visa, J., Soriano, E., Estivill, X., & Arbonés, M. L. (2002). Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. Molecular and Cellular Biology, 22(18), 6636-6647. https://doi.org/10.1128/MCB.22.18.6636-6647.2002