Multi-influential genetic interactions alter behaviour and cognition through six main biological cascades in Down syndrome mouse models.

Autor:	Duchon A; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Del Mar Muniz Moreno M; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Martin Lorenzo S; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Silva de Souza MP; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Chevalier C; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Nalesso V; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Meziane H; Université de Strasbourg, CNRS, INSERM, Institut Clinique de la Souris (ICS), CELPHEDIA, PHENOMIN, 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Loureiro de Sousa P; Université de Strasbourg, CNRS UMR 7357, ICube, FMTS, 67000 Strasbourg, France., Noblet V; Université de Strasbourg, CNRS UMR 7357, ICube, FMTS, 67000 Strasbourg, France., Armspach JP; Université de Strasbourg, CNRS UMR 7357, ICube, FMTS, 67000 Strasbourg, France., Brault V; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France., Herault Y; Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), department of translational medicine and neurogenetics 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France.; Université de Strasbourg, CNRS, INSERM, Institut Clinique de la Souris (ICS), CELPHEDIA, PHENOMIN, 1 rue Laurent Fries, 67404 Illkirch Graffenstaden, France.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2021 May 28; Vol. 30 (9), pp. 771-788.
DOI:	10.1093/hmg/ddab012
Abstrakt:	Down syndrome (DS) is the most common genetic form of intellectual disability caused by the presence of an additional copy of human chromosome 21 (Hsa21). To provide novel insights into genotype-phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging and hippocampal gene expression to screen several DS mouse models for the mouse chromosome 16 region homologous to Hsa21. First, we unravelled several genetic interactions between different regions of chromosome 16 and how they contribute significantly to altering the outcome of the phenotypes in brain cognition, function and structure. Then, in-depth analysis of misregulated expressed genes involved in synaptic dysfunction highlighted six biological cascades centred around DYRK1A, GSK3β, NPY, SNARE, RHOA and NPAS4. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms targeting specific hubs in DS models that should become central to better understanding of DS and improving the development of therapies. (© The Author(s) 2021. Published by Oxford University Press.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu