PT - JOURNAL ARTICLE AU - Karl Obrietan AU - Kari R. Hoyt TI - CRE-Mediated Transcription Is Increased in Huntington's Disease Transgenic Mice AID - 10.1523/JNEUROSCI.3493-03.2004 DP - 2004 Jan 28 TA - The Journal of Neuroscience PG - 791--796 VI - 24 IP - 4 4099 - http://www.jneurosci.org/content/24/4/791.short 4100 - http://www.jneurosci.org/content/24/4/791.full SO - J. Neurosci.2004 Jan 28; 24 AB - Disruption of cAMP response element (CRE)-dependent transcription has been hypothesized to contribute to neuronal death and dysfunction in Huntington's disease (HD) and other polyglutamine repeat disorders. Whether dysregulation of CRE-dependent transcription actually occurs in vivo in response to expression of expanded polyglutamine repeats has not been tested. We directly tested whether CRE-dependent transcription is affected in vivo by cross breeding a transgenic mouse model of HD (line R6/2) with a transgenic mouse that expresses a CRE-regulated reporter gene. Instead of compromised CRE-dependent transcription in HD mice, we found a robust upregulation of CRE-dependent transcription in several brain regions (striatum, hippocampus, cortex). CRE-mediated transcription was also evoked by striatal forskolin infusion and by photic stimulation in HD animals. Increased cAMP response element-binding protein (CREB) phosphorylation and elevated levels of the CREB-regulated gene product, CCAAT/enhancer binding protein β, were also found in HD mice. Significant alterations in CREB binding protein expression and localization were not observed in symptomatic R6/2 mice. Thus, rather than repressing CRE-mediated transcription, mutant huntingtin appears to facilitate transcription via a CRE-dependent mechanism in vivo.