scholarly journals Lifespan analysis of brain development, gene expression and behavioral phenotypes in the Ts1Cje, Ts65Dn and Dp(16)1/Yey mouse models of Down syndrome

2018 ◽  
Vol 11 (6) ◽  
pp. dmm031013 ◽  
Author(s):  
Nadine M. Aziz ◽  
Faycal Guedj ◽  
Jeroen L. A. Pennings ◽  
Jose Luis Olmos-Serrano ◽  
Ashley Siegel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Brain Development ◽  
Mouse Models ◽  
Behavioral Phenotypes

Decrease in the T-box1 gene expression in embryonic brain and adult hippocampus of down syndrome mouse models

2021 ◽  
Vol 535 ◽  
pp. 87-92
Author(s):  
Ryohei Shimizu ◽  
Keiichi Ishihara ◽  
Eri Kawashita ◽  
Haruhiko Sago ◽  
Kazuhiro Yamakawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Mouse Models ◽  
Embryonic Brain ◽  
Adult Hippocampus

scholarly journals Potential Role of JAK-STAT Signaling Pathway in the Neurogenic-to-Gliogenic Shift in Down Syndrome Brain

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Han-Chung Lee ◽  
Kai-Leng Tan ◽  
Pike-See Cheah ◽  
King-Hwa Ling
Keyword(s):  
Down Syndrome ◽  
Brain Development ◽  
Cell Fate ◽  
Mouse Models ◽  
Neuronal Cell ◽  
Janus Kinase ◽  
Chromosome 21 ◽  
Severe Intellectual Disability ◽  
Stat Signaling

Trisomy of human chromosome 21 in Down syndrome (DS) leads to several phenotypes, such as mild-to-severe intellectual disability, hypotonia, and craniofacial dysmorphisms. These are fundamental hallmarks of the disorder that affect the quality of life of most individuals with DS. Proper brain development involves meticulous regulation of various signaling pathways, and dysregulation may result in abnormal neurodevelopment. DS brain is characterized by an increased number of astrocytes with reduced number of neurons. In mouse models for DS, the pool of neural progenitor cells commits to glia rather than neuronal cell fate in the DS brain. However, the mechanism(s) and consequences of this slight neurogenic-to-gliogenic shift in DS brain are still poorly understood. To date, Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling has been proposed to be crucial in various developmental pathways, especially in promoting astrogliogenesis. Since both human and mouse models of DS brain exhibit less neurons and a higher percentage of cells with astrocytic phenotypes, understanding the role of JAK-STAT signaling in DS brain development will provide novel insight into its role in the pathogenesis of DS brain and may serve as a potential target for the development of effective therapy to improve DS cognition.

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.

scholarly journals Genes Associated with Disturbed Cerebral Neurogenesis in the Embryonic Brain of Mouse Models of Down Syndrome

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1598
Author(s):  
Keiichi Ishihara
Keyword(s):  
Down Syndrome ◽  
Intellectual Disability ◽  
Brain Development ◽  
Candidate Genes ◽  
Mouse Models ◽  
Trisomy 21 ◽  
Embryonic Brain ◽  
Cortical Neurogenesis ◽  
Chromosomal Engineering ◽  
Impaired Neurogenesis

Down syndrome (DS), also known as trisomy 21, is the most frequent genetic cause of intellectual disability. Although the mechanism remains unknown, delayed brain development is assumed to be involved in DS intellectual disability. Analyses with human with DS and mouse models have shown that defects in embryonic cortical neurogenesis may lead to delayed brain development. Cre-loxP-mediated chromosomal engineering has allowed the generation of a variety of mouse models carrying various partial Mmu16 segments. These mouse models are useful for determining genotype–phenotype correlations and identifying dosage-sensitive genes involved in the impaired neurogenesis. In this review, we summarize several candidate genes and pathways that have been linked to defective cortical neurogenesis in DS.

scholarly journals Multi-influential interactions alters behaviour and cognition through six main biological cascades in Down syndrome mouse models

2020 ◽  
Author(s):  
Arnaud Duchon ◽  
Maria del Mar Muñiz Moreno ◽  
Sandra Martin Lorenzo ◽  
Márcia Priscilla Silva de Souza ◽  
Claire Chevalier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Down Syndrome ◽  
Mouse Models ◽  
Brain Function ◽  
Molecular Mechanisms ◽  
Chromosome 21 ◽  
List Type ◽  
Depth Analysis ◽  
Altered Gene

AbstractDown syndrome (DS) is the most common genetic form of intellectual disability caused by the presence of an additional copy of human chromosome 21. To provide novel insights into genotype–phenotype correlations, we screened the in vivo DS mouse library with standardized behavioural tests, magnetic resonance imaging (MRI) and hippocampal gene expression. Altogether this approach brings novel insights into the field. First, we unravelled several genetic interactions between different regions of the chromosome 21 and how they importantly contribute in altering the outcome of the phenotypes in brain function and structure. Then, in depth analysis of misregulated expressed genes involved in synaptic dysfunction highlitghed 6 biological cascades centered around DYRK1A, GSK3β, NPY, SNARE, RHOA and NPAS4. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms targeting specific hubs in DS models that should become central to advance in our understanding of DS and therapies development.HighlightsBrain function and morphology changes in DS mouse models result from multiple genetic lociEach combination of loci induces specific alteration of gene expression profile in mouse modelsAltered gene expression converges to a few functional pathwys in DS mouse hippocampiThe synaptic pathway analysis leads to six connected biological cascades and defines a specific DS disease network

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