Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

SUBMITTER: Duchon A

PROVIDER: S-EPMC8161522 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-17 | GSE149470 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (TgDyrk1a)

Project description:Down syndrome (DS) is the most common genetic form of intellectual disability with additional clinical features, caused by the presence of an additional copy of human chromosome 21 (Hsa21). A few number of patients with DS features, carry partial duplication of Hsa21 and their study provided novel insights into genotype–phenotype correlations. Despite the progress of genome analysis, the rareness of patients with partial duplication, and the human genetic heterogeneity, makes difficult to achieve a more detailed phenotypic map at present. As a complementary approach, we screened the in vivo DS mouse library with highly standardized behavioural tests, magnetic resonance imaging (MRI) and digged into hippocampal gene expression to go further in dissecting the genotype–phenotype correlations and in deciphering misregulated genes, functional pathways and biological cascades in DS models. Altogether this approach bring novel insights into the field. First, we unravelled the complexity of the genetic interactions between different regions of the chromosome 21 and how they play an important role in modulating the outcome of the behavioural and molecular phenotypes. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed six biological cascades centered around DYRK1A, GSK3beta, NPY, RHOA, NPAS4 and the SNARE complex. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms that could be at play for both the DS clinical features and the rescue mechanisms by targeting specific hubs or well connected nodes that may be central to advance in our understanding of DS and therapies development.

2021-03-17 | GSE149464 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (Ts65Dn)

2021-03-17 | GSE149465 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (Dp1Yey)

2021-03-17 | GSE149460 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (Dp5Yah)

2021-03-17 | GSE149463 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (Dp5Dp1)

2021-03-17 | GSE149462 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (Dp3Yah)

2021-03-17 | GSE149461 | GEO

Multi-influential interactions controls behaviour and cognition through a limited number of pathways in Down syndrome mouse models (Dp1Rhr)