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Regnier V , Billard JM , Gupta S , Potier B , Woerner S , Paly E , Ledru A , David S , Luilier S , Bizot JC , Vacano G , Kraus JP , Patterson D , Kruger WD , Delabar JM , London J
Brain Phenotype of Transgenic Mice Overexpressing Cystathionine beta-Synthase
Plos One. 2012 Jan;7(1) :e29056
PMID: WOS:000301357100005 PMCID: PMC3257219
AbstractBackground: The cystathionine beta-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological processes. Methodology/Principal Findings: Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a similar to 2-fold increase in total CBS proteins in different brain areas and a similar to 1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line. Conclusion/Significance: We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS.
NotesRegnier, Vinciane Billard, Jean-Marie Gupta, Sapna Potier, Brigitte Woerner, Stephanie Paly, Evelyne Ledru, Aurelie David, Sabrina Luilier, Sabrina Bizot, Jean-Charles Vacano, Guido Kraus, Jan P. Patterson, David Kruger, Warren D. Delabar, Jean M. London, Jaqueline Fondation Jerome Lejeune; European Commission; National Institutes of Health (NIH)[HD17449, HL50299, CA06927]; Hempling Foundation This work was supported by the Fondation Jerome Lejeune (to DP, JL, VR, JPK); the European Commission (anEUploidy, 037627 to J-CB, JMD); and the National Institutes of Health (NIH) (HD17449 to DP). SG and WK were supported in part by the NIH (HL50299, CA06927), the Hempling Foundation, and an appropriation from the Commonwealth of Pennsylvania to the Fox Chase Cancer Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. 69 Public library science San francisco 906oy