Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase
Abstract
Background: The cystathionine b-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 ,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.
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.
Origin : Publication funded by an institution
