Genomes and Genes
Affiliation: Center for Genomic Regulation
- Down syndrome: the brain in trisomic modeMara Dierssen
Genes and Disease Programme, Centre for Genomic Regulation CRG, Universitat Pompeu Fabra, Centro de Investigación Biomédica en Red de Enfermedades Raras, E 08003 Barcelona, Spain
Nat Rev Neurosci 13:844-58. 2012..These advances hold promise for the development of treatments for intellectual disability...
- Alterations of neocortical pyramidal cell phenotype in the Ts65Dn mouse model of Down syndrome: effects of environmental enrichmentM Dierssen
Program in Genes and Disease, Genomic Regulation Center, Passeif Maritim 32 49, 08003 Barcelona, Spain
Cereb Cortex 13:758-64. 2003..The present results suggest that behavioral deficits demonstrated in the Ts65Dn model could be attributed to abnormal circuit development...
- Aneuploidy: from a physiological mechanism of variance to Down syndromeMara Dierssen
Genes and Disease Program, Genomic Regulation Center CRG, Pompeu Fabra University, Barcelona Biomedical Research Park, Dr Aiguader 88, PRBB building E, Barcelona 08003, Catalonia, Spain
Physiol Rev 89:887-920. 2009..We also review the potential that genetically engineered mouse models of DS bring into the understanding of the molecular biology of human learning disorders...
- DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): a gene with dosage effect during development and neurogenesisM Dierssen
Genes and Disease Program, Genomic Regulation Center, Barcelona Biomedical Research Park, 08003 Barcelona, Spain
ScientificWorldJournal 6:1911-22. 2006..This review focuses on the functional role that DYRK1A plays in brain development...
- Behavioral characterization of a mouse model overexpressing DSCR1/ RCAN1Mara Dierssen
Centre for Genomic Regulation, Barcelona Biomedical Research Park, and CIBER de Enfermedades Raras, Barcelona, Catalonia, Spain
PLoS ONE 6:e17010. 2011....
- Transgenic mice overexpressing the full-length neurotrophin receptor TrkC exhibit increased catecholaminergic neuron density in specific brain areas and increased anxiety-like behavior and panic reactionMara Dierssen
Genes and Disease Program, Genomic Regulation Center CRG UPF, Barcelona, Biomedical Research Park, E 08003 Barcelona, Catalonia, Spain
Neurobiol Dis 24:403-18. 2006..Our results demonstrate that the elevated NT3-TrkC tone via overexpression of TrkC in the brain may constitute a molecular mechanism for the expression of anxiety and anxiety...
- Dendritic pathology in mental retardation: from molecular genetics to neurobiologyM Dierssen
Neurobehavioral Analysis Laboratory, Genes and Disease Program, Center for Genomic Regulation, CRG UPF PRBB, 08003 Barcelona, Spain
Genes Brain Behav 5:48-60. 2006..In this review, we discuss the neurobiology underlying MR, with a focus on FraX and DS...
- Overexpression of the CHRNA5/A3/B4 genomic cluster in mice increases the sensitivity to nicotine and modifies its reinforcing effectsXavier Gallego
Genes and Disease Program, Center for Genomic Regulation, Barcelona Biomedical Research Park, 08003 Barcelona, Catalonia, Spain
Amino Acids 43:897-909. 2012....
- Targeting Dyrk1A with AAVshRNA attenuates motor alterations in TgDyrk1A, a mouse model of Down syndromeJon Ortiz-Abalia
Programa Gens i Malaltia Centre de Regulació Genòmica CRG, UPF, Parc de Recerca Biomédica de Barcelona PRBB, Barcelona 08003, Spain
Am J Hum Genet 83:479-88. 2008..Furthermore, these results identify Dyrk1A as a potential target for therapy in DS...
- Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A)Gloria Arqué
Genes and Disease Program, Genomic Regulation Center CRG, Pompeu Fabra University, Barcelona, Spain
PLoS ONE 3:e2575. 2008..It encodes a dual-specificity kinase involved in neuronal development and in adult brain physiology, but its possible role as critical haploinsufficient gene in cognitive function has not been explored...
- Normalization of Dyrk1A expression by AAV2/1-shDyrk1A attenuates hippocampal-dependent defects in the Ts65Dn mouse model of Down syndromeXavier Altafaj
Centre for Biomedical Network Research on Rare Diseases, Barcelona, Spain
Neurobiol Dis 52:117-27. 2013..Taken together, these results show Dyrk1A as a critical player in the pathophysiology of DS and define Dyrk1A as a therapeutic target in adult trisomic mice...
- Susceptibility to stress in transgenic mice overexpressing TrkC, a model of panic disorderAlejandro Amador-Arjona
Genes and Disease Program, Centre for Genomic Regulation, Universidad Pompeu Fabra, Barcelona Biomedical Research Park PRBB, Dr Aiguader 88, Barcelona E 08003, Spain
J Psychiatr Res 44:157-67. 2010....
- Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse modelMonica Santos
Systems Biology Programme, Centre for Genomic Regulation, E 08003 Barcelona, Spain, Universitat Pompeu Fabra, E 08003 Barcelona, Spain, Centro de Investigación Biomédica en Red de Enfermedades Raras, E 08003 Barcelona, Spain, Department of Stem Cells and Regeneration, Sanford Burnham Medical Research Institute, La Jolla, California 92037, and Institute of Biology, Otto von Guericke University Magdeburg, and Center for Behavioral Brain Sciences, D39120 Magdeburg, Germany
J Neurosci 33:15259-71. 2013..The fearful phenotype appears to be the result of hippocampal hyperexcitability and aberrant fear circuit activation. We conclude that NTRK3 plays a role in PAND by regulating hippocampus-dependent fear memories. ..
- Overexpression of α3/α5/β4 nicotinic receptor subunits modifies impulsive-like behaviorXavier Viñals
Laboratory of Neuropharmacology, Pompeu Fabra University, PRBB, Barcelona, Spain
Drug Alcohol Depend 122:247-52. 2012..These results reveal the involvement of α3/α5/β4 nicotinic receptor subunits in working memory and impulsivity, two behavioral traits directly related to the vulnerability to develop nicotine dependence...
- Age-associated motor and visuo-spatial learning phenotype in Dyrk1A heterozygous mutant miceGloria Arqué
Genes and Disease Program, Center for Genomic Regulation CRG, Pompeu Fabra University, Barcelona Biomedical Research Park PRBB and CIBER de Enfermedades Raras CIBERER, Barcelona, Spain
Neurobiol Dis 36:312-9. 2009....
- Aberrant brain microRNA target and miRISC gene expression in the anx/anx anorexia mouse modelJosep M Mercader
Center for Genomic Regulation, Barcelona, Catalonia, Spain
Gene 497:181-90. 2012....
- Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous systemEulalia Marti
Program in Genes and Disease, Centre de Regulacio Genomica CRG, Passeig Maritim 37 49, 08003, Barcelona, Spain
Brain Res 964:250-63. 2003....
- Hypothalamus transcriptome profile suggests an anorexia-cachexia syndrome in the anx/anx mouse modelJosep Maria Mercader
Genes and Disease Program, Center for Genomic Regulation CRG UPF, Barcelona, Catalonia, Spain
Physiol Genomics 35:341-50. 2008....
- Insights from mouse models to understand neurodegeneration in Down syndromeCristina Fillat
Centre de Regulacio Genomica, UPF, Parc de Recerca Biomedica de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras, Spain
CNS Neurol Disord Drug Targets 9:429-38. 2010..In addition, these models might allow to define and evaluate potential drug targets and to develop therapeutic strategies that may interfere or delay the onset of AD...
- Dissociation between CA3-CA1 synaptic plasticity and associative learning in TgNTRK3 transgenic miceIgnasi Sahún
Genes and Disease Program, Genomic Regulation Center, Universidad Pompeu Fabra, Barcelona Biomedical Research Park, 08003 Barcelona, Spain
J Neurosci 27:2253-60. 2007..No changes of AMPA and kainate subunits were detected. Results indicate that the NT-3/TrkC cascade could regulate synaptic transmission and plasticity through modulation of glutamatergic transmission at the CA3-CA1 synapse...
- Pitfalls and hopes in Down syndrome therapeutic approaches: in the search for evidence-based treatmentsMara Dierssen
Genes and Disease Program, Genomic Regulation Center, CRG UPF, Barcelona Biomedical Research Park, Spain
Behav Genet 36:454-68. 2006..We describe some of the most recent developments in the field and give a sense of the prospects for future prevention and therapy...
- Overexpression of Reelin prevents the manifestation of behavioral phenotypes related to schizophrenia and bipolar disorderCátia M Teixeira
Developmental Neurobiology and Regeneration Unit, Institute for Research in Biomedicine, Parc Cientific de Barcelona, University of Barcelona, Barcelona, Spain
Neuropsychopharmacology 36:2395-405. 2011..Together, these results point to the Reelin signaling pathway as a relevant drug target for the treatment of a range of psychiatric disorders...
- Association of NTRK3 and its interaction with NGF suggest an altered cross-regulation of the neurotrophin signaling pathway in eating disordersJosep Maria Mercader
Genes and Disease Program, Center for Genomic Regulation, 08003 Barcelona, Catalonia, Spain
Hum Mol Genet 17:1234-44. 2008..The reported data, in addition to the previous reported findings for BDNF and NTRK2, point neurotrophin signaling genes as key regulators of eating behavior and their altered cross-regulation as susceptibility factors for EDs...
- Motor phenotypic alterations in TgDyrk1a transgenic mice implicate DYRK1A in Down syndrome motor dysfunctionM Martinez de Lagran
Programme of Genes and Disease, Center for Genomic Regulation, 08003 Barcelona, Spain
Neurobiol Dis 15:132-42. 2004..These results confirm and extend previous data and provide further insight to the functional domains that might be altered in TgDyrk1a mice and underlying molecular mechanisms of DS motor dysfunction...
- Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in miceVassiliki Fotaki
Medical and Molecular Genetics Center, Institut de Recerca Oncologica, 08907 L Hospitalet de Llobregat, Barcelona, Spain
Mol Cell Biol 22:6636-47. 2002..These data provide evidence about the nonredundant, vital role of Dyrk1A and suggest a conserved mode of action that determines normal growth and brain size in both mice and flies...
- Synthetic zinc finger repressors reduce mutant huntingtin expression in the brain of R6/2 miceMireia Garriga-Canut
EMBL CRG Systems Biology Research Unit, Centre for Genomic Regulation CRG, Dr Aiguader 88, 08003 Barcelona, Spain
Proc Natl Acad Sci U S A 109:E3136-45. 2012....
- Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndromeX Altafaj
Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, Gran Via s n, Km 2 7, 08907 L Hospitalet de Llobregat, Barcelona, Catalonia, Spain
Hum Mol Genet 10:1915-23. 2001..These alterations are comparable with those found in the partial trisomy chromosome 16 murine models of DS and suggest a causative role of DYRK1A in mental retardation and in motor anomalies of DS...
- Functional implications of hippocampal adult neurogenesis in intellectual disabilitiesMeritxell Pons-Espinal
Systems Biology Program, Centre for Genomic Regulation CRG, Dr Aiguader 88, 08003 Barcelona, Spain
Amino Acids 45:113-31. 2013..We review the process of generating functional neurons from precursors in the adult brain and its implications in intellectual disability disorders...
- Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: possible role in Down syndromeGloria Arqué
Genes and Disease Program, Center for Genomic Regulation CRG, Pompeu Fabra University, Barcelona Biomedical Research Park PRBB and CIBER de Enfermedades Raras CIBERER, Barcelona, Spain
PLoS ONE 8:e54285. 2013....
- Targeting the endocannabinoid system in the treatment of fragile X syndromeArnau Busquets-Garcia
Departament de Ciències Experimentals i de la Salut DCEXS, Universitat Pompeu Fabra UPF, Barcelona, Spain
Nat Med 19:603-7. 2013..Some of these traits were also reversed by pharmacological inhibition of mTOR or mGluR5. Thus, blockade of ECS is a potential therapeutic approach to normalize specific alterations in FXS...
- Transgenic over expression of nicotinic receptor alpha 5, alpha 3, and beta 4 subunit genes reduces ethanol intake in miceXavier Gallego
Genes and Disease Program, Center for Genomic Regulation, UPF, Barcelona, Spain
Alcohol 46:205-15. 2012..water) preference test. These results suggest a complex role for this receptor subunit gene cluster in the modulation of ethanol's as well as nicotine's effects...
- Increased opioid dependence in a mouse model of panic disorderXavier Gallego
Genes and Disease Program, Genomic Regulation Center CRG, Barcelona Biomedical Research Park PRBB and CIBER de Enfermedades Raras Barcelona, Catalonia, Spain
Front Behav Neurosci 3:60. 2010....
- Increased NR2A expression and prolonged decay of NMDA-induced calcium transient in cerebellum of TgDyrk1A mice, a mouse model of Down syndromeX Altafaj
Programa Gens i Malatia, Centre de Regulacio Genomica CRG, UPF, Parc de Recerca Biomédica de Barcelona PRBB, Barcelona, Spain
Neurobiol Dis 32:377-84. 2008..These findings suggest that DYRK1A overexpression might contribute to the dysbalance in the excitatory transmission found in the cerebellum of DS individuals and DS mouse models...
- DNA methylation map of mouse and human brain identifies target genes in Alzheimer's diseaseJose V Sanchez-Mut
1 Cancer Epigenetics and Biology Program PEBC, Bellvitge Biomedical Research Institute IDIBELL, 08908 L Hospitalet, Barcelona, Catalonia, Spain
Brain 136:3018-27. 2013..These hypermethylation targets indicate that the cyclic AMP response element-binding protein (CREB) activation pathway and the axon initial segment could contribute to the disease. ..
- Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1AMeritxell Pons-Espinal
Systems Biology Program, Centre for Genomic Regulation CRG, Dr Aiguader 88, E 08003 Barcelona, Spain Universitat Pompeu Fabra UPF, Dr Aiguader 88, E 08003 Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras CIBERER, Dr Aiguader 88, E 08003 Barcelona, Spain
Neurobiol Dis 60:18-31. 2013....
- Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and futureRafael de la Torre
Neurosciences Research Programme, IMIM Hospital del Mar Research Institute and CIBEROBN, Barcelona, Spain
Prog Brain Res 197:1-14. 2012..Epigallocatechin gallate, a green tea polyphenol, that modulates DYRK1A functioning has already shown preliminarily that this approach may prove useful in therapeutics...
- Reduced Mid1 Expression and Delayed Neuromotor Development in daDREAM Transgenic MiceMara Dierssen
Genomic Regulation Center, Parc de Recerca Biomedica de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Raras Barcelona, Spain
Front Mol Neurosci 5:58. 2012..As a consequence, daDREAM mice exhibit a significant shortening of the rostro-caudal axis of the cerebellum and a delay in neuromotor development early after birth. Our results indicate a role for DREAM in cerebellar function...
- Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2G Azkona
Genes and Disease Program, Center for Genomic Regulation CRG, Barcelona Biomedical Research Park PRBB, E 08003 Barcelona, Catalonia, Spain
Genes Brain Behav 9:160-72. 2010..However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression...
- Murine models for Down syndromeM Dierssen
Down Syndrome Research Group, Medical and Molecular Genetics Center IRO, Hospital Duran i Reynals, Granvia km 2 7, 08907 L Hospitalet de Llobregat, Barcelona, Spain
Physiol Behav 73:859-71. 2001..Here we review the existing murine models and the relevance of their contribution to DS research...
- Dopaminergic deficiency in mice with reduced levels of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A, Dyrk1A(+/-)M Martinez de Lagran
Genes and Disease Program, Center for Genomic Regulation, CRG UPF PRBB, Barcelona, Spain
Genes Brain Behav 6:569-78. 2007..These data indicate that Dyrk1A is essential for a proper function of nigrostriatal dopaminergic neurons and suggest that Dyrk1A(+/-) mice can be used to study the pathogenesis of motor disorders involving dopaminergic dysfunction...
- Haploinsufficiency of Dyrk1A in mice leads to specific alterations in the development and regulation of motor activityV Fotaki
Genetics and Disease Program, Genomic Regulation Center, Barcelona, Spain
Behav Neurosci 118:815-21. 2004..These results are in agreement with the significant expression of Dyrk1A in structures related to motor function and support a role of Dyrk1A in the control of motor function...
- Differential responses to anxiogenic drugs in a mouse model of panic disorder as revealed by Fos immunocytochemistry in specific areas of the fear circuitryI Sahún
Genes and Disease Program, Center for Genomic Regulation CRG, Barcelona Biomedical Research Park PRBB, Barcelona, Spain
Amino Acids 33:677-88. 2007....
- Candidate genes for panic disorder: insight from human and mouse genetic studiesM Gratacos
Genes and Disease Program, Genomic Regulation Center CRG, Pompeu Fabra University, Barcelona Biomedical Research Park, Barcelona, Catalonia, Spain
Genes Brain Behav 6:2-23. 2007..The integration of human and animal studies targeting behavioral, systems-level, cellular and molecular levels will most probably help identify new molecules with potential impact on the pathogenetic aspects of the disease...
- Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+/- mouseR Benavides-Piccione
Cajal Institute, Av Dr Arce, 37, 28002 Madrid, Spain
Neurobiol Dis 20:115-22. 2005..These results suggest that Dyrk1A influences the size and complexity of pyramidal cells, and thus their capability to integrate information...
- Reduced phospholipase C-beta activity and isoform expression in the cerebellum of TS65Dn mouse: a model of Down syndromeI Ruiz de Azua
Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country, Alava, Spain
J Neurosci Res 66:540-50. 2001....
- Down syndrome and the genes of human chromosome 21: current knowledge and future potentials. Report on the Expert workshop on the biology of chromosome 21 genes: towards gene-phenotype correlations in Down syndrome. Washington D.C., September 28-October 1M Pritchard
Monash University, Victoria, Australia
Cytogenet Genome Res 121:67-77. 2008..A knowledge-based approach to therapeutics also requires the correlation of chromosome 21 gene function with phenotypic features...
- On dendrites in Down syndrome and DS murine models: a spiny way to learnR Benavides-Piccione
Cajal Institute, 28002 Madrid, Spain
Prog Neurobiol 74:111-26. 2004....
- Brain G protein-dependent signaling pathways in Down syndrome and Alzheimer's diseaseM Lumbreras
Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain
Amino Acids 31:449-56. 2006..Our results demonstrate that PLC and AC were severely disturbed in the aged DS and AD brains, but the alterations in DS were more severe, and differed to some extent from those observed in AD...
- Postnatal handling induces long-term modifications in central beta-noradrenergic signalling in ratsC Baamonde
Laboratory of Developmental Neurobiology, Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Avda Herrera Oria, S N, 39011 Santander, Spain
Stress 5:137-47. 2002..These results suggest that the long-lasting adaptation of the adenylyl cyclase transduction system, which affects the primary biochemical response of the beta-adrenoceptor, may participate in the effects of this manipulation...
- Protein expression of BACE1, BACE2 and APP in Down syndrome brainsM S Cheon
Department of Pediatrics, Medical University of Vienna, Vienna, Austria
Amino Acids 35:339-43. 2008..Furthermore, current data indicate that the DS phenotype cannot be fully explained by simple gene dosage effect...