Behavioral Characterization of a Mouse Model Overexpressing DSCR1/ RCAN1

Abstract

DSCR1/ RCAN1 is a chromosome 21 gene found to be overexpressed in the brains of Down syndrome (DS) and postulated as a good candidate to contribute to mental disability. However, even though Rcan1 knockout mice have pronounced spatial learning and memory deficits, the possible deleterious effects of its overexpression in DS are not well understood. We have generated a transgenic mouse model overexpressing DSCR1/RCAN1 in the brain and analyzed the effect of RCAN1 overexpression on cognitive function. TgRCAN1 mice present a marked disruption of the learning process in a visuo-spatial learning task. However, no significant differences were observed in the performance of the memory phase of the test (removal session) nor in a step-down passive avoidance task, thus suggesting that once learning has been established, the animals are able to consolidate the information in the longer term.

Fish oil improves gene targets of Down syndrome in C57BL and BALB/c mice

“…Nonetheless, the combined overexpression of RCAN1 and DYRK1A has now been identified as a possible key contributor to some phenotypes of Down syndrome etiology [20,[22][23][24][25]. We believe that a simple, healthy, and cost-effective approach to treating Down syndrome (and possibly associated Alzheimer) is to identify nutraceuticals that reduce RCAN1 and DYRK1A levels, in turn, activating NF-AT signaling (usually represented by NF-AT dephosphorylation).…”

“…One such chromosome 21 gene is RCAN1 (regulator of calcineurin 1). This gene has become one of the leading candidates for contributing to some (but not all) phenotypes of Down syndrome [19][20][21][22][23][24]. RCAN1 has also been implicated in Alzheimer disease, and early-onset Alzheimer disease is a much higher risk in Down syndrome [19,23,24].…”

Molecular Genetics of Intellectual Disability

“…Following these positive outcomes, a human clinical trial has been recently completed, although no results have been published so far (NCT01394796). A more recent mouse model, TgRCAN1, also highlighted the impact of the overexpression of DSCR1 (RCAN1), a functional inhibitor of calcineurin, in visuo-spatial learning and memory tasks similar to those present in Down syndrome affected persons (Dierssen et al, 2011). Other studies exploring the hypothesis of high levels of inhibition being involved in Down syndrome cognitive dysfunction also revealed promising results.…”

Avances Citogenéticos y Neurobiológicos en el Síndrome de Down

“…Specifically, it has been found a relationship between the overexpression of these genes and the emergence of alterations in brain plasticity, in the neuronal branches extension and cerebral apoptosis processes. And as to the behavioral characteristics it has been found a link between these genes and alterations in spatial learning, acquisition of locomotion or the exploratory behavior (Altafaj et al, 2001;Chrast et al, 2000;Dierssen et al, 2011;Donato, 2003;Lopes, Chettouh, Delabar & Rachidi, 2003;Martínez et al, 2008;Park et al, 2009;Yabut, Domagauer & D"Arcangelo, 2010).…”