title: Loss of MeCP2 in Parvalbumin-and Somatostatin-Expressing Neurons in Mice Leads to Distinct Rett Syndrome-like Phenotypes.
abstract: Inhibitory neurons are critical for proper brain function, and their dysfunction is implicated in several disorders, including autism, schizophrenia, and Rett syndrome. These neurons are heterogeneous, and it is unclear which subtypes contribute to specific neurological phenotypes. We deleted Mecp2, the mouse homolog of the gene that causes Rett syndrome, from the two most populous subtypes, parvalbumin-positive (PV+) and somatostatin-positive (SOM+) neurons. Loss of MeCP2 partially impairs the affected neuron, allowing us to assess the function of each subtype without profound disruption of neuronal circuitry. We found that mice lacking MeCP2 in either PV+ or SOM+ neurons have distinct, non-overlapping neurological features: mice lacking MeCP2 in PV+ neurons developed motor, sensory, memory, and social deficits, whereas those lacking MeCP2 in SOM+ neurons exhibited seizures and stereotypies. Our findings indicate that PV+ and SOM+ neurons contribute complementary aspects of the Rett phenotype and may have modular roles in regulating specific behaviors.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Aya
authors.initials: A
authors.lastname: Ito-Ishida
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Ure
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Swann
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA; Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA. Electronic address: hzoghbi@bcm.edu.
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D055786:Gene Knockout Techniques; D008568:Memory; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism*; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics*; D012640:Seizures / Q000235:genetics; D012677:Sensation / Q000235:genetics; D012919:Social Behavior; D013004:Somatostatin / Q000378:metabolism*; D013239:Stereotyped Behavior
chemical_list: C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2; D010320:Parvalbumins; D013004:Somatostatin