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Proteomic analysis of DYRK1A-knockin mice

ABSTRACT: Dyrk1A deficiency is linked to various neurodevelopmental disorders, including developmental delays and autism spectrum disorders (ASD). Haploinsufficiency of Dyrk1a in mice leads to ASD-related phenotypes, although key pathological mechanisms remain unclear. In addition, human DYRK1A mutations have not been characterized in mice. Here we report Dyrk1a-knockin mice carrying a human mutation (Ile48LysfsX2; Dyrk1a-I48K mice). These mice display severe microcephaly, social and cognitive deficits, dendritic shrinkage, excitatory synaptic deficits, and altered phospho-proteome patterns enriched for multiple signaling pathways and synaptic proteins. Early chronic lithium treatment of newborn mutant mice rescues brain volume, behavior, dendrite, synapse, and signaling/synapse phospho-proteome phenotypes at juvenile and adult stages. These results suggest that signaling/synaptic alterations contribute to phenotypic alterations in Dyrk1a-I48K mice, and that early correction of these alterations by lithium treatment has long-lasting effects of preventing juvenile and adult-stage phenotypes.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Jin Young Kim

PROVIDER: MSV000094073 | MassIVE | Tue Feb 13 18:23:00 GMT 2024

SECONDARY ACCESSION(S): PXD049356

REPOSITORIES: MassIVE

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