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DYRK1A is the human orthologue of the Drosophila minibrain (mnb) gene, which is involved in postembryonic neurogenesis in flies. Because of its mapping position on chromosome 21 and the neurobehavioral alterations shown by mice overexpressing this gene, involvement of DYRK1A in some of the neurological defects of Down syndrome patients has been suggested.(More)
The availability of the recently published DNA sequence of human chromosome 21 (HSA21) is a landmark contribution that will have an immediate impact on the study of the role of specific genes to Down syndrome (DS). Trisomy 21 or DS is the only autosomal aneuploidy that is not lethal in the fetal or early postnatal period. DS phenotypes show variable(More)
Oxidative stress (OS) underlies neuronal dysfunction in many neurodegenerative disorders. Regulator of Calcineurin 1 (RCAN1 or DSCR1) is a dose-sensitive gene whose overexpression has been linked to Down syndrome (DS) and Alzheimer's disease (AD) neuropathology and to the response of cells to stress stimuli. Here, we show that RCAN1 mRNA and protein(More)
BACKGROUND Pathogenic aneuploidies involve the concept of dosage-sensitive genes leading to over- and underexpression phenotypes. Monosomy 21 in human leads to mental retardation and skeletal, immune and respiratory function disturbances. Most of the human condition corresponds to partial monosomies suggesting that critical haploinsufficient genes may be(More)
People with Down syndrome (DS) exhibit abnormal brain structure. Alterations affecting neurotransmission and signalling pathways that govern brain function are also evident. A large number of genes are simultaneously expressed at abnormal levels in DS; therefore, it is a challenge to determine which gene(s) contribute to specific abnormalities, and then(More)
The subplate layer of the cerebral cortex is comprised of a heterogeneous population of cells and contains some of the earliest-generated neurons. In the embryonic brain, subplate cells contribute to the guidance and areal targeting of thalamocortical axons. At later developmental stages, they are predominantly involved in the maturation and plasticity of(More)
Genes located on chromosome 21, over-expressed in Down syndrome (DS) and Alzheimer's disease (AD) and which regulate vesicle trafficking, are strong candidates for involvement in AD neuropathology. Regulator of calcineurin activity 1 (RCAN1) is one such gene. We have generated mutant mice in which RCAN1 is either over-expressed (RCAN1(ox)) or ablated(More)
DYRK1A is a protein kinase proposed to be involved in neurogenesis. Gene-targeting disruption of Dyrk1A in mice leads to decreased body and brain size, with no severe disturbance of behavior. In this study, the authors focused on the motor profile of Dyrk1A(+/-) mice. These mice presented impairment of neuromotor development with decreased activity,(More)
Several connexin genes (GJB1, GJB2, GJB3, GJB6 and GJA1) have been found mutated in patients with non-syndromic and/or syndromic deafness indicating an important role of these proteins in the auditory system. In order to better understand the function of the connexins in the inner ear we have analyzed the gene expression profiles of two connexin genes, Gjb1(More)
We have demonstrated that DSCR1 acts as a negative regulator of calcineurin-mediated signaling and that its transcript is overexpressed in the Down syndrome (DS) fetal brain. To evaluate the possible involvement of DSCR1 in DS, we have cloned the mouse gene and analyzed its expression pattern in the central nervous system (CNS). Early expression of Dscr1 is(More)