Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene expression.

摘要: Receptor-interacting protein 140 (RIP140) is a negative transcriptional coregulator of nuclear receptors such as estrogen, retinoic acid or glucocorticoid receptors. Recruitment RIP140 results in an inhibition target gene expression through different repressive domains interacting with histone deacetylases C-terminal binding proteins. In this study, we analyzed the role activity memory processes using RIP140-deficient transgenic mice. Although was clearly expressed brain (cortical and hippocampus areas), morphological examination RIP140−/− mouse failed to show grossly observable alterations. Using male 2-month-old RIP140−/−, RIP140+/− RIP140+/+ mice, did not observe any significant differences open-field test, rotarod test terms spontaneous alternation Y-maze. By contrast, mice showed long-term deficits, absence decrease escape latencies when animals were tested fixed platform position procedure water maze passive avoidance test. Noteworthy, decreased swimming speed, suggesting alterations that may part account for marked measured maze. Moreover, increase immobility time forced compared wild-type animals. These observations depletion learning deficits well stress response, bringing light major neurophysiological developmental mechanisms underlying cognitive functions.