Targeting Dyrk1A with AAVshRNA Attenuates Motor Alterations in TgDyrk1A, a Mouse Model of Down Syndrome

Hattori, 2000, The DNA sequence of human chromosome 21, Nature, 405, 311, 10.1038/35012518 Antonarakis, 2006, The challenge of Down syndrome, Trends Mol. Med., 12, 473, 10.1016/j.molmed.2006.08.005 Dowjat, 2007, Trisomy-driven overexpression of DYRK1A kinase in the brain of subjects with Down syndrome, Neurosci. Lett., 413, 77, 10.1016/j.neulet.2006.11.026 Guimera, 1999, Human minibrain homologue (MNBH/DYRK1): Characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome, Genomics, 57, 407, 10.1006/geno.1999.5775 Becker, 1998, Sequence characteristics, subcellular localization, and substrate specificity of DYRK-related kinases, a novel family of dual specificity protein kinases, J. Biol. Chem., 273, 25893, 10.1074/jbc.273.40.25893 Dierssen, 2006, DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): A gene with dosage effect during development and neurogenesis, ScientificWorldJournal, 6, 1911, 10.1100/tsw.2006.319 Smith, 1997, Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome, Nat. Genet., 16, 28, 10.1038/ng0597-28 Martinez de Lagran, 2004, Motor phenotypic alterations in TgDyrk1a transgenic mice implicate DYRK1A in Down syndrome motor dysfunction, Neurobiol. Dis., 15, 132, 10.1016/j.nbd.2003.10.002 Ahn, 2006, DYRK1A BAC transgenic mice show altered synaptic plasticity with learning and memory defects, Neurobiol. Dis., 22, 463, 10.1016/j.nbd.2005.12.006 Altafaj, 2001, Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down's syndrome, Hum. Mol. Genet., 10, 1915, 10.1093/hmg/10.18.1915 Arron, 2006, NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21, Nature, 441, 595, 10.1038/nature04678 Warrington, 2006, Treatment of human disease by adeno-associated viral gene transfer, Hum. Genet., 119, 571, 10.1007/s00439-006-0165-6 Sui, 2002, A DNA vector-based RNAi technology to suppress gene expression in mammalian cells, Proc. Natl. Acad. Sci. USA, 99, 5515, 10.1073/pnas.082117599 Fujita, 1999, Coactivation of secretogranin-II and BDNF genes mediated by calcium signals in mouse cerebellar granule cells, Brain Res. Mol. Brain Res., 63, 316, 10.1016/S0169-328X(98)00299-X Marti, 2003, Dyrk1A expression pattern supports specific roles of this kinase in the adult central nervous system, Brain Res., 964, 250, 10.1016/S0006-8993(02)04069-6 Salvetti, 1998, Factors influencing recombinant adeno-associated virus production, Hum. Gene Ther., 9, 695, 10.1089/hum.1998.9.5-695 Brooks, 2004, Transcriptional silencing is associated with extensive methylation of the CMV promoter following adenoviral gene delivery to muscle, J. Gene Med., 6, 395, 10.1002/jgm.516 McBride, 2008, Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: Implications for the therapeutic development of RNAi, Proc. Natl. Acad. Sci. USA, 105, 5868, 10.1073/pnas.0801775105 Campbell, 2007, Primary and secondary neural networks of auditory prepulse inhibition: A functional magnetic resonance imaging study of sensorimotor gating of the human acoustic startle response, Eur. J. Neurosci., 26, 2327, 10.1111/j.1460-9568.2007.05858.x Geyer, 2001, Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: A decade in review, Psychopharmacology (Berl.), 156, 117, 10.1007/s002130100811 Fernandez, 2007, Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome, Nat. Neurosci., 10, 411, 10.1038/nn1860 Costa, 2008, Acute injections of the NMDA receptor antagonist memantine rescue performance deficits of the Ts65Dn mouse model of Down syndrome on a fear conditioning test, Neuropsychopharmacology, 33, 1624, 10.1038/sj.npp.1301535 Fotaki, 2002, Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice, Mol. Cell. Biol., 22, 6636, 10.1128/MCB.22.18.6636-6647.2002 Fotaki, 2004, Haploinsufficiency of Dyrk1A in mice leads to specific alterations in the development and regulation of motor activity, Behav. Neurosci., 118, 815, 10.1037/0735-7044.118.4.815 Tejedor, 1995, minibrain: A new protein kinase family involved in postembryonic neurogenesis in Drosophila, Neuron, 14, 287, 10.1016/0896-6273(95)90286-4 Moller, 2008, Truncation of the Down syndrome candidate gene DYRK1A in two unrelated patients with microcephaly, Am. J. Hum. Genet., 82, 1165, 10.1016/j.ajhg.2008.03.001 Okui, 1999, High-level expression of the Mnb/Dyrk1A gene in brain and heart during rat early development, Genomics, 62, 165, 10.1006/geno.1999.5998 Martinez de Lagran, 2007, Dopaminergic deficiency in mice with reduced levels of the dual-specificity tyrosine-phosphorylated and regulated kinase 1A, Dyrk1A(+/−), Genes Brain Behav., 6, 569, 10.1111/j.1601-183X.2006.00285.x Hallett, 2006, Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking, J. Neurosci., 26, 4690, 10.1523/JNEUROSCI.0792-06.2006