Manipulations of MeCP2 in glutamatergic neurons highlight their contributions to Rett and other neurological disorders.
Many postnatal onset neurological disorders such as autism spectrum disorders (ASDs) and intellectual disability are thought to arise largely from disruption of excitatory/inhibitory homeostasis. Although mouse models of Rett syndrome (RTT), a postnatal neurological disorder caused by loss-of-function mutations in MECP2, display impaired excitatory neurotransmission, the RTT phenotype can be largely reproduced in mice simply by removing MeCP2 from inhibitory GABAergic neurons. To determine what role excitatory signaling impairment might play in RTT pathogenesis, we generated conditional mouse models with Mecp2 either removed from or expressed solely in glutamatergic neurons. MeCP2 deficiency in glutamatergic neurons leads to early lethality, obesity, tremor, altered anxiety-like behaviors, and impaired acoustic startle response, which is distinct from the phenotype of mice lacking MeCP2 only in inhibitory neurons. These findings reveal a role for excitatory signaling impairment in specific neurobehavioral abnormalities shared by RTT and other postnatal neurological disorders.
Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
Xiangling
X
Meng
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
Wei
W
Wang
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.
Hui
H
Lu
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
Ling-Jie
LJ
He
Department of Neuroscience, Baylor College of Medicine, Houston, United States.|The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
Wu
W
Chen
Department of Neuroscience, Baylor College of Medicine, Houston, United States.|The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
Eugene S
ES
Chao
Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, United States.
Marta L
ML
Fiorotto
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Department of Pediatrics, Baylor College of Medicine, Houston, United States.
Bin
B
Tang
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, United States.
Jose A
0000-0003-3808-1769
JA
Herrera
Huffington Center on Aging, Baylor College of Medicine, Houston, United States.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.
Michelle L
ML
Seymour
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
Jeffrey L
JL
Neul
Huffington Center on Aging, Baylor College of Medicine, Houston, United States.|Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.|Bobby R Alford Department of Otolaryngology - Head and Neck Surgery, Baylor College of Medicine, Houston, United States.
Fred A
FA
Pereira
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Department of Pediatrics, Baylor College of Medicine, Houston, United States.
Jianrong
J
Tang
Department of Neuroscience, Baylor College of Medicine, Houston, United States.|The Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.
Mingshan
M
Xue
Department of Neuroscience, Baylor College of Medicine, Houston, United States.|Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, United States.|Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States.|Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States.
Huda Y
0000-0002-0700-3349
HY
Zoghbi
D000818:Animals; D015870:Gene Expression; D051783:Methyl-CpG-Binding Protein 2 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology*; D009474:Neurons / Q000502:physiology*
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2
MeCP2; Rett syndrome; glutamatergic neurons; mouse; neurological disorders; neuroscience