Article ; Online: Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model.
2023 Volume 190, Page(s) 106359
Abstract: Aberrant neurodevelopment in Down syndrome (DS)-caused by triplication of human chromosome 21-is commonly attributed to gene dosage imbalance, linking overexpression of trisomic genes with disrupted developmental processes, with DYRK1A particularly ... ...
| Abstract | Aberrant neurodevelopment in Down syndrome (DS)-caused by triplication of human chromosome 21-is commonly attributed to gene dosage imbalance, linking overexpression of trisomic genes with disrupted developmental processes, with DYRK1A particularly implicated. We hypothesized that regional brain DYRK1A protein overexpression in trisomic mice varies over development in sex-specific patterns that may be distinct from Dyrk1a transcription, and reduction of Dyrk1a copy number from 3 to 2 in otherwise trisomic mice reduces DYRK1A, independent of other trisomic genes. DYRK1A overexpression varied with age, sex, and brain region, with peak overexpression on postnatal day (P) 6 in both sexes. Sex-dependent differences were also evident from P15-P24. Reducing Dyrk1a copy number confirmed that these differences depended on Dyrk1a gene dosage and not other trisomic genes. Trisomic Dyrk1a mRNA and protein expression were not highly correlated. Sex-specific patterns of DYRK1A overexpression during trisomic neurodevelopment may provide mechanistic targets for therapeutic intervention in DS. |
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| MeSH term(s) | Animals ; Female ; Humans ; Male ; Mice ; Brain/metabolism ; Disease Models, Animal ; Down Syndrome/genetics ; Down Syndrome/metabolism ; Mice, Transgenic ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/genetics ; Protein-Tyrosine Kinases/metabolism | |||||
| Chemical Substances | Protein Serine-Threonine Kinases (EC 2.7.11.1) ; Protein-Tyrosine Kinases (EC 2.7.10.1) ; Dyrk1a protein, mouse (EC 2.7.1.-) | |||||
| Language | English | |||||
| Publishing date | 2023-11-20 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1211786-9 | |||||
| ISSN | 1095-953X ; 0969-9961 | |||||
| ISSN (online) | 1095-953X | |||||
| ISSN | 0969-9961 | |||||
| DOI | 10.1016/j.nbd.2023.106359 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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