scholarly journals Effects of early-life exposure to THIP on brainstem neuronal excitability in the Mecp2 -null mouse model of Rett syndrome before and after drug withdrawal

2017 ◽  
Vol 5 (2) ◽  
pp. e13110 ◽  
Author(s):  
Weiwei Zhong ◽  
Christopher M. Johnson ◽  
Ningren Cui ◽  
Max F. Oginsky ◽  
Yang Wu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Early Life ◽  
Neuronal Excitability ◽  
Drug Withdrawal ◽  
Null Mouse ◽  
Early Life Exposure ◽  
Before And After

scholarly journals Effects of early-life exposure to THIP on phenotype development in a mouse model of Rett syndrome

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Weiwei Zhong ◽  
Christopher Mychal Johnson ◽  
Yang Wu ◽  
Ningren Cui ◽  
Hao Xing ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Early Life ◽  
Early Life Exposure

scholarly journals Severe changes in colon epithelium in the Mecp2-null mouse model of Rett syndrome

2016 ◽  
Vol 3 (1) ◽  
Author(s):  
Pamela Millar-Büchner ◽  
Amber R. Philp ◽  
Noemí Gutierrez ◽  
Sandra Villanueva ◽  
Bredford Kerr ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Null Mouse

scholarly journals Microglia contribute to circuit defects in Mecp2 null mice independent of microglia-specific loss of Mecp2 expression

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Dorothy P Schafer ◽  
Christopher T Heller ◽  
Georgia Gunner ◽  
Molly Heller ◽  
Christopher Gordon ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Neural Circuits ◽  
Neurodevelopmental Disorder ◽  
Cell Types ◽  
Null Mouse ◽  
Causative Role ◽  
Specific Loss ◽  
Synapse Loss ◽  
Circuit Defects

Microglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder<xref ref-type="bibr" rid="bib19"/><xref ref-type="bibr" rid="bib15"/><xref ref-type="bibr" rid="bib37"/><xref ref-type="bibr" rid="bib47"/>. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role<xref ref-type="bibr" rid="bib67"/>. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2tm1.1Bird/y). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease (≥P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss or gain of Mecp2 expression specifically in microglia (Cx3cr1CreER;Mecp2fl/yor Cx3cr1CreER; Mecp2LSL/y) had little effect on excessive engulfment, synapse loss, or phenotypic abnormalities. Taken together, our data suggest that microglia contribute to end stages of disease by dismantling neural circuits rendered vulnerable by loss of Mecp2 in other CNS cell types.

Lung abnormalities in MECP2-null mouse model of Rett syndrome

2017 ◽  
Vol 381 ◽  
pp. 923
Author(s):  
H. Kida ◽  
T. Takahashi ◽  
Y. Nakamura ◽  
T. Kinoshita ◽  
S. Okayama ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Null Mouse ◽  
Lung Abnormalities

scholarly journals Pharmacological read-through of R294X Mecp2 in a novel mouse model of Rett syndrome

2020 ◽  
Vol 29 (15) ◽  
pp. 2461-2470
Author(s):  
Jonathan K Merritt ◽  
Bridget E Collins ◽  
Kirsty R Erickson ◽  
Hongwei Dong ◽  
Jeffrey L Neul
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Therapeutic Approach ◽  
Neurodevelopmental Disorder ◽  
Intraperitoneal Administration ◽  
Full Length ◽  
Nonsense Suppression ◽  
Null Mouse ◽  
Peripheral Tissues ◽  
Mecp2 Protein

Abstract Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in Methyl-CpG-binding Protein 2 (MECP2). More than 35% of affected individuals have nonsense mutations in MECP2. For these individuals, nonsense suppression has been suggested as a possible therapeutic approach. To assess the viability of this strategy, we created and characterized a mouse model with the common p.R294X mutation introduced into the endogenous Mecp2 locus (Mecp2R294X). Mecp2R294X mice exhibit phenotypic abnormalities similar to those seen in complete null mouse models; however, these occur at a later time point consistent with the reduced phenotypic severity seen in affected individuals containing this specific mutation. The delayed onset of severe phenotypes is likely due to the presence of truncated MeCP2 in Mecp2R294X mice. Supplying the MECP2 transgene in Mecp2R294X mice rescued phenotypic abnormalities including early death and demonstrated that the presence of truncated MeCP2 in these mice does not interfere with wild-type MeCP2. In vitro treatment of a cell line derived from Mecp2R294X mice with the nonsense suppression agent G418 resulted in full-length MeCP2 protein production, demonstrating feasibility of this therapeutic approach. Intraperitoneal administration of G418 in Mecp2R294X mice was sufficient to elicit full-length MeCP2 protein expression in peripheral tissues. Finally, intracranial ventricular injection of G418 in Mecp2R294X mice induced expression of full-length MeCP2 protein in the mouse brain. These experiments demonstrate that translational read-through drugs are able to suppress the Mecp2 p.R294X mutation in vivo and provide a proof of concept for future preclinical studies of nonsense suppression agents in RTT.

Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome

2006 ◽  
Vol 21 (1) ◽  
pp. 217-227 ◽  
Author(s):  
Yukiko Asaka ◽  
Denis G.M. Jugloff ◽  
Liang Zhang ◽  
James H. Eubanks ◽  
Reiko Maki Fitzsimonds
Keyword(s):  
Synaptic Plasticity ◽  
Mouse Model ◽  
Rett Syndrome ◽  
Null Mouse ◽  
Hippocampal Synaptic Plasticity

scholarly journals Pathogenesis of Lethal Aspiration Pneumonia in Mecp2-null Mouse Model for Rett Syndrome

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hiroshi Kida ◽  
Tomoyuki Takahashi ◽  
Yuki Nakamura ◽  
Takashi Kinoshita ◽  
Munetsugu Hara ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Aspiration Pneumonia ◽  
Null Mouse

scholarly journals Alterations of Gene Expression and Glutamate Clearance in Astrocytes Derived from an MeCP2-Null Mouse Model of Rett Syndrome

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e35354 ◽  
Author(s):  
Yasunori Okabe ◽  
Tomoyuki Takahashi ◽  
Chiaki Mitsumasu ◽  
Ken-ichiro Kosai ◽  
Eiichiro Tanaka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Rett Syndrome ◽  
Null Mouse
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