Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism.
Rett syndrome, a neurodevelopmental X-linked disorder, represents the most important genetic cause of severe mental retardation in the female population and results from a mutation in the gene encoding methyl-CpG-binding protein 2 (MECP2). We report here the first characterization of Mecp2-null mice, by in vivo magnetic resonance imaging and spectroscopy, delineating the cerebral phenotype associated with the lack of Mecp2. We performed a morphometric study that revealed a size reduction of the whole brain and of structures involved in cognitive and motor functions (cerebellum and motor cortex). Significant metabolic anomalies, including reduced N-acetylaspartate, myo-inositol, and glutamine plus glutamate, and increased choline levels were evidenced. These findings indicate that not only neuronal but also glial metabolism is affected in Mecp2-null mice. Furthermore, we uncovered an important reduction of brain ATP level, a hitherto undetected anomaly of energy metabolism that may reflect and contribute to cerebral injury and dysfunction.
Saywell
Véronique
V
INSERM U491, Faculté de Médecine la Timone, Marseille, France.
Viola
Angèle
A
Confort-Gouny
Sylviane
S
Le Fur
Yann
Y
Villard
Laurent
L
Cozzone
Patrick J
PJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002794:Choline / Q000378:metabolism; D018899:CpG Islands; D004734:Energy Metabolism; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010641:Phenotype
D051783:Methyl-CpG-Binding Protein 2; D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; D000255:Adenosine Triphosphate; C000179:N-acetylaspartate; D002794:Choline