title: Brain phenotype of transgenic mice overexpressing cystathionine β-synthase.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unité de Biologie Fonctionnelle et Adaptative, CNRS EAC 4413, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. vinciane.regnier@univ-paris-diderot.fr
authors.forename: Vinciane
authors.initials: V
authors.lastname: Régnier
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Billard
authors.forename: Sapna
authors.initials: S
authors.lastname: Gupta
authors.forename: Brigitte
authors.initials: B
authors.lastname: Potier
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Woerner
authors.forename: Evelyne
authors.initials: E
authors.lastname: Paly
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ledru
authors.forename: Sabrina
authors.initials: S
authors.lastname: David
authors.forename: Sabrina
authors.initials: S
authors.lastname: Luilier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Bizot
authors.forename: Guido
authors.initials: G
authors.lastname: Vacano
authors.forename: Jan P
authors.initials: JP
authors.lastname: Kraus
authors.forename: David
authors.initials: D
authors.lastname: Patterson
authors.forename: Warren D
authors.initials: WD
authors.lastname: Kruger
authors.forename: Jean M
authors.initials: JM
authors.lastname: Delabar
authors.forename: Jaqueline
authors.initials: J
authors.lastname: London
mesh_terms: D000603:Amino Acids, Sulfur / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000502:physiology*; D003541:Cystathionine beta-Synthase / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010641:Phenotype; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D019076:Transgenes / Q000235:genetics
chemical_list: D000603:Amino Acids, Sulfur; D003541:Cystathionine beta-Synthase