Behavioral Characterization of a Mouse Model Overexpressing DSCR1/ RCAN1

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.

• Publication year

  2011

• Venue

  PLoS ONE

• Publication date

  2011-02-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0017010PMID 21364922PMCID 3045383
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2009influential reference
• Impaired Spatial Learning Strategies and Novel Object Recognition in Mice Haploinsufficient for the Dual Specificity Tyrosine-Regulated Kinase-1A (Dyrk1A)

  2008cited by this paper
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  2008cited by this paper
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  2007cited by this paper
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  2004cited by this paper
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  2003cited by this paper
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  2002cited by this paper
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  2001cited by this paper
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  2001cited by this paper
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  2000cited by this paper
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  2000cited by this paper
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  1998influential reference
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  1998cited by this paper
• Cosmid contig and transcriptional map of three regions of human chromosome 21q22: identification of 37 novel transcripts by direct selection.

  1997cited by this paper
• A behavioral assessment of Ts65Dn mice: a putative Down syndrome model.

  1995influential reference
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  1993cited by this paper
• Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element.

  1993cited by this paper
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  1992cited by this paper
• PDGF B-chain in neurons of the central nervous system, posterior pituitary, and in a transgenic model.

  1991cited by this paper

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  2019cites this paper
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  2017cites this paper
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  2016cites this paper
• Developmental exposure to paraquat and maneb can impair cognition, learning and memory in Sprague-Dawley rats.

  2016cites this paper
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  2016cites this paper
• RCAN1 overexpression promotes age-dependent mitochondrial dysregulation related to neurodegeneration in Alzheimer’s disease

  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015influential citation
• Dendritic spine dysgenesis in autism related disorders.

  2015cites this paper
• Evidence of long-term gene flow and selection during domestication from analyses of Eurasian wild and domestic pig genomes

  2015cites this paper
• Cytogenetic and Neurobiological Advances in Down syndrome

  2014cites this paper
• Aberrant Expression of RCAN1 in Alzheimer’s Pathogenesis: A New Molecular Mechanism and a Novel Drug Target

  2014cites this paper
• Overexpression of RCAN1 isoform 4 in mouse neurons leads to a moderate behavioral impairment

  2013cites this paper
• Chapter 30 – Down Syndrome

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  2013cites this paper
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  2012cites this paper
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  2012cites this paper
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