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Mental retardation in Down syndrome (DS), the most frequent trisomy in humans, varies from moderate to severe. Several studies both in human and based on mouse models identified some regions of human chromosome 21 (Hsa21) as linked to cognitive deficits. However, other intervals such as the telomeric region of Hsa21 may contribute to the DS phenotype but(More)
Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available(More)
The function of the majority of genes in the mouse and human genomes remains unknown. The mouse embryonic stem cell knockout resource provides a basis for the characterization of relationships between genes and phenotypes. The EUMODIC consortium developed and validated robust methodologies for the broad-based phenotyping of knockouts through a pipeline(More)
Fibroblasts are the major mesenchymal cell type in connective tissue and deposit the collagen and elastic fibres of the extracellular matrix (ECM). Even within a single tissue, fibroblasts exhibit considerable functional diversity, but it is not known whether this reflects the existence of a differentiation hierarchy or is a response to different(More)
Trisomy 21 is the most frequent genetic cause of cognitive impairment. To assess the perturbations of gene expression in trisomy 21, and to eliminate the noise of genomic variability, we studied the transcriptome of fetal fibroblasts from a pair of monozygotic twins discordant for trisomy 21. Here we show that the differential expression between the twins(More)
Down syndrome (DS) is the most frequent genetic disorder leading to intellectual disabilities and is caused by three copies of human chromosome 21. Mouse models are widely used to better understand the physiopathology in DS or to test new therapeutic approaches. The older and the most widely used mouse models are the trisomic Ts65Dn and the Ts1Cje mice.(More)
Cognitive deficits in Down syndrome (DS) have been linked to increased synaptic inhibition, leading to an imbalance of excitation/inhibition (E/I). Various mouse models and studies from human brains have implicated an HSA21 gene, the serine/threonine kinase DYRK1A, as a candidate for inducing cognitive dysfunction. Here, consequences of alterations in(More)
The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in(More)
Trisomy 21 or Down syndrome (DS) is the most common form of human aneuploid disorder. Increase in the copy number of human chromosome 21 genes leads to several alterations including mental retardation, heart and skeletal dysmorphologies with additional physiological defects. To better understand the genotype and phenotype relationships, several mouse models(More)
Quantitative differences in gene expression emerge as a significant source of variation in natural populations, representing an important substrate for evolution and accounting for a considerable fraction of phenotypic diversity. However, perturbation of gene expression is also the main factor in determining the molecular pathogenesis of numerous aneuploid(More)