scholarly journals A MYT1L syndrome mouse model recapitulates patient phenotypes and reveals altered brain development due to disrupted neuronal maturation

Neuron ◽  
2021 ◽  
Author(s):  
Jiayang Chen ◽  
Mary E. Lambo ◽  
Xia Ge ◽  
Joshua T. Dearborn ◽  
Yating Liu ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Development ◽  
Neuronal Maturation

scholarly journals Brain Development and Heart Function after Systemic Single-Agent Chemotherapy in a Mouse Model of Childhood Leukemia Treatment

2018 ◽  
Vol 24 (23) ◽  
pp. 6040-6052 ◽  
Author(s):  
T. Leigh Spencer Noakes ◽  
Thomas S. Przybycien ◽  
Amanda Forwell ◽  
Connor Nicholls ◽  
Yu-Qing Zhou ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Development ◽  
Childhood Leukemia ◽  
Heart Function ◽  
Single Agent ◽  
Leukemia Treatment ◽  
Single Agent Chemotherapy

Transcriptional repressor REST drives lineage stage–specific chromatin compaction atPtch1and increases AKT activation in a mouse model of medulloblastoma

2019 ◽  
Vol 12 (565) ◽  
pp. eaan8680 ◽  
Author(s):  
Tara H. W. Dobson ◽  
Rong-Hua Tao ◽  
Jyothishmathi Swaminathan ◽  
Shinji Maegawa ◽  
Shavali Shaik ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transcriptional Repressor ◽  
Negative Regulator ◽  
Neuronal Maturation ◽  
Cerebellar Granule Neuron ◽  
Akt Activation ◽  
Shh Pathway ◽  
Histone Modifiers ◽  
Induced Apoptosis ◽  
Context Specific

In medulloblastomas (MBs), the expression and activity of RE1-silencing transcription factor (REST) is increased in tumors driven by the sonic hedgehog (SHH) pathway, specifically the SHH-α (children 3 to 16 years) and SHH-β (infants) subgroups. Neuronal maturation is greater in SHH-β than SHH-α tumors, but both correlate with poor overall patient survival. We studied the contribution of REST to MB using a transgenic mouse model (RESTTG) wherein conditionalNeuroD2-controlledRESTtransgene expression in lineage-committedPtch1+/−cerebellar granule neuron progenitors (CGNPs) accelerated tumorigenesis and increased penetrance and infiltrative disease. This model revealed a neuronal maturation context–specific antagonistic interplay between the transcriptional repressor REST and the activator GLI1 atPtch1. Expression ofArrb1, which encodes β-arrestin1 (a GLI1 inhibitor), was substantially reduced in proliferating and, to a lesser extent, lineage-committedRESTTGcells compared with wild-type proliferating CGNPs. Lineage-committedRESTTGcells also had decreased GLI1 activity and increased histone H3K9 methylation at thePtch1locus, which correlated with premature silencing ofPtch1. These cells also had decreased expression ofPten, which encodes a negative regulator of the kinase AKT. Expression ofPTCH1andGLI1were less, andARRB1was somewhat greater, in patient SHH-β than SHH-α MBs, whereas that ofPTENwas similarly lower in both subtypes than in others. Inhibition of histone modifiers or AKT reduced proliferation and induced apoptosis, respectively, in cultured REST-high MB cells. Our findings linking REST to differentiation-specific chromatin remodeling,PTCH1silencing, and AKT activation in MB tissues reveal potential subgroup-specific therapeutic targets for MB patients.

Pharmacotherapy with sertraline rescues brain development and behavior in a mouse model of CDKL5 deficiency disorder

2020 ◽  
Vol 167 ◽  
pp. 107746 ◽  
Author(s):  
Claudia Fuchs ◽  
Laura Gennaccaro ◽  
Elisa Ren ◽  
Giuseppe Galvani ◽  
Stefania Trazzi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Development ◽  
And Behavior

scholarly journals SMN deficiency disrupts brain development in a mouse model of severe spinal muscular atrophy

2010 ◽  
Vol 19 (21) ◽  
pp. 4216-4228 ◽  
Author(s):  
Thomas M. Wishart ◽  
Jack P.-W. Huang ◽  
Lyndsay M. Murray ◽  
Douglas J. Lamont ◽  
Chantal A. Mutsaers ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Brain Development ◽  
Muscular Atrophy

Inbred mouse model of brain development and intestinal microbiota

2021 ◽  
pp. 545-555
Author(s):  
Reinaldo B. Oriá ◽  
Daniel V. Pinto ◽  
Ronaldo P. Dias ◽  
Ramon S. Raposo ◽  
Patricia L. Foley ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Development ◽  
Intestinal Microbiota ◽  
Inbred Mouse

scholarly journals Assessing the requirements of prenatal UBE3A expression for rescue of behavioral phenotypes in a mouse model for Angelman syndrome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Monica Sonzogni ◽  
Peipei Zhai ◽  
Edwin J. Mientjes ◽  
Geeske M. van Woerden ◽  
Ype Elgersma
Keyword(s):  
Gene Expression ◽  
Mouse Model ◽  
Brain Development ◽  
Mouse Brain ◽  
Angelman Syndrome ◽  
Neurodevelopmental Disorder ◽  
Brain Regions ◽  
Critical Function ◽  
Behavioral Phenotypes ◽  
Mouse Brain Development

Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental disorder caused by the loss of functional ubiquitin protein ligase E3A (UBE3A). In neurons, UBE3A expression is tightly regulated by a mechanism of imprinting which suppresses the expression of the paternal UBE3A allele. Promising treatment strategies for AS are directed at activating paternal UBE3A gene expression. However, for such strategies to be successful, it is important to know when such a treatment should start, and how much UBE3A expression is needed for normal embryonic brain development. Methods Using a conditional mouse model of AS, we further delineated the critical period for UBE3A expression during early brain development. Ube3a gene expression was induced around the second week of gestation and mouse phenotypes were assessed using a behavioral test battery. To investigate the requirements of embryonic UBE3A expression, we made use of mice in which the paternal Ube3a allele was deleted. Results We observed a full behavioral rescue of the AS mouse model phenotypes when Ube3a gene reactivation was induced around the start of the last week of mouse embryonic development. We found that full silencing of the paternal Ube3a allele was not completed till the first week after birth but that deletion of the paternal Ube3a allele had no significant effect on the assessed phenotypes. Limitations Direct translation to human is limited, as we do not precisely know how human and mouse brain development aligns over gestational time. Moreover, many of the assessed phenotypes have limited translational value, as the underlying brain regions involved in these tasks are largely unknown. Conclusions Our findings provide further important insights in the requirement of UBE3A expression during brain development. We found that loss of up to 50% of UBE3A protein during prenatal mouse brain development does not significantly impact the assessed mouse behavioral phenotypes. Together with previous findings, our results indicate that the most critical function for mouse UBE3A lies in the early postnatal period between birth and P21.

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