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Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase
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Edité par CCSD ; Public Library of Science -
International audience. Background: The cystathionine b-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate forplaying a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and itencodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brainphysiological processes.Methodology/Principal Findings: Here, we have studied the neural consequences of CBS overexpression in a transgenicmouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. Thesemice displayed a ,2-fold increase in total CBS proteins in different brain areas and a ,1.3-fold increase in CBS activity in thecerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic miceshowed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synapticplasticity is facilitated in the 60.4P102D1 line.Conclusion/Significance: We demonstrate that CBS overexpression has functional consequences on hippocampal neuronalnetworks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBSoverexpression might have an advantageous effect on some cognitive functions in DS.
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