Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase
by Vinciane Régnier, Jean-Marie Billard, Sapna Gupta, Brigitte Potier, Stéphanie Woerner, Evelyne Paly, Aurélie Ledru, Sabrina David, Sabrina Luilier, Jean-Charles Bizot, Guido Vacano, Jan P. Kraus, David Patterson, Warren D. Kruger, Jean M. Delabar, Jaqueline London
The cystathionine β-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.
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 ∼2-fold increase in total CBS proteins in different brain areas and a ∼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.
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.
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