Regulación de la respuesta génica al dolor por el represor transcripcional dream

Résumé

The DREAM protein (Downstream regulatory element antagonist modulator) protein regulates gene expresion by direct binding to DNA in a Ca2+-dependent manner. To investigate the function of DREAM in vivo, we have prepared and characterized several lines of transgenic mice which overespress a calcium insensitive EF-hand mutant DREAM (EFmDREAM). Both in vitro and vivo, EFmDREAM functions a dominant active mutant (daDREAM) blocking calcium-mediated de-repression of target genes. Overexpression of daDREAM in the CNS resulted in an increase of the nociceptive response in several pain models. This findig correlates with the the important reduction in the opioid tone in daDREAM mice with a significant decrease in the expression of all three opioid receptors as well as dynorphines. Comparative gene profiling analisys of daDREAM revealed important differences in genetic response compared with wild type mice. The pattern of gene expression in daDREAM is similar to the chronic pain model gene expression pattern.