scholarly journals OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome

2019 ◽  
Vol 24 (6) ◽  
pp. 908-926.e8 ◽  
Author(s):  
Ranjie Xu ◽  
Andrew T. Brawner ◽  
Shenglan Li ◽  
Jing-Jing Liu ◽  
Hyosung Kim ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Models ◽  
Chimeric Mouse ◽  
Human Ipsc

scholarly journals OLIG2 Drives Abnormal Neurodevelopmental Phenotypes in Human iPSC-Based Organoid and Chimeric Mouse Models of Down Syndrome

2018 ◽  
Author(s):  
Ranjie Xu ◽  
Andrew T Brawner ◽  
Shenglan Li ◽  
JingJing Liu ◽  
Hyosung Kim ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Early Stage ◽  
Neurodevelopmental Disorder ◽  
Neural Progenitors ◽  
Chimeric Mouse ◽  
Chimeric Mice ◽  
Neurodevelopmental Abnormalities ◽  
Induced Pluripotent ◽  
Human Ipsc ◽  
Cognitive Defects

SUMMARYDown syndrome (DS) is a common neurodevelopmental disorder, and cognitive defects in DS patients may arise form imbalances in excitatory and inhibitory neurotransmission. Understanding the mechanisms underlying such imbalances may provide opportunities for therapeutic intervention. Here, we show that human induced pluripotent stem cells (hiPSCs) derived from DS patients overproduce OLIG2+ ventral forebrain neural progenitors. As a result, DS hiPSC-derived cerebral organoids excessively produce specific subclasses of GABAergic interneurons and cause impaired recognition memory in neuronal chimeric mice. Increased OLIG2 expression in DS cells directly upregulates interneuron lineage-determining transcription factors. shRNA-mediated knockdown of OLIG2 largely reverses abnormal gene expression in early-stage DS neural progenitors, reduces interneuron production in DS organoids and chimeric mouse brains, and improves behavioral deficits in DS chimeric mice. Thus, altered OLIG2 expression may underlie neurodevelopmental abnormalities and cognitive defects in DS patients.

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 Social Factors Influence Behavior in the Novel Object Recognition Task in a Mouse Model of Down Syndrome

2021 ◽  
Vol 15 ◽  
Author(s):  
Cesar Sierra ◽  
Ilario De Toma ◽  
Lorenzo Lo Cascio ◽  
Esteban Vegas ◽  
Mara Dierssen
Keyword(s):  
Down Syndrome ◽  
Object Recognition ◽  
Environmental Factors ◽  
Mouse Models ◽  
Recognition Task ◽  
Novel Object Recognition ◽  
The Novel ◽  
Wild Type ◽  
Male And Female ◽  
Novel Object

The use of mouse models has revolutionized the field of Down syndrome (DS), increasing our knowledge about neuropathology and helping to propose new therapies for cognitive impairment. However, concerns about the reproducibility of results in mice and their translatability to humans have become a major issue, and controlling for moderators of behavior is essential. Social and environmental factors, the experience of the researcher, and the sex and strain of the animals can all have effects on behavior, and their impact on DS mouse models has not been explored. Here we analyzed the influence of a number of social and environmental factors, usually not taken into consideration, on the behavior of male and female wild-type and trisomic mice (the Ts65Dn model) in one of the most used tests for proving drug effects on memory, the novel object recognition (NOR) test. Using principal component analysis and correlation matrices, we show that the ratio of trisomic mice in the cage, the experience of the experimenter, and the timing of the test have a differential impact on male and female and on wild-type and trisomic behavior. We conclude that although the NOR test is quite robust and less susceptible to environmental influences than expected, to obtain useful results, the phenotype expression must be contrasted against the influences of social and environmental factors.

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

scholarly journals Perturbation of the immune cells and prenatal neurogenesis by the triplication of the Erg gene in mouse models of Down syndrome

2019 ◽  
Vol 30 (1) ◽  
pp. 75-91 ◽  
Author(s):  
Keiichi Ishihara ◽  
Ryohei Shimizu ◽  
Kazuyuki Takata ◽  
Eri Kawashita ◽  
Kenji Amano ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Models ◽  
Immune Cells

scholarly journals Quantitative Analysis of Retinal Structure and Function in Two Chromosomally Altered Mouse Models of Down Syndrome

2020 ◽  
Vol 61 (5) ◽  
pp. 25
Author(s):  
Daniella B. Victorino ◽  
Jonah J. Scott-McKean ◽  
Mark W. Johnson ◽  
Alberto C. S. Costa
Keyword(s):  
Down Syndrome ◽  
Quantitative Analysis ◽  
Mouse Models ◽  
Structure And Function ◽  
Retinal Structure ◽  
And Function

scholarly journals Aging rather than aneuploidy affects monoamine neurotransmitters in brain regions of Down syndrome mouse models

2017 ◽  
Vol 105 ◽  
pp. 235-244 ◽  
Author(s):  
Alain D. Dekker ◽  
Yannick Vermeiren ◽  
Christelle Albac ◽  
Eva Lana-Elola ◽  
Sheona Watson-Scales ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Models ◽  
Brain Regions ◽  
Monoamine Neurotransmitters

On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models

2001 ◽  
Vol 35 (2) ◽  
pp. 115-145 ◽  
Author(s):  
Zygmunt Galdzicki ◽  
Richard Siarey ◽  
Rosalyn Pearce ◽  
James Stoll ◽  
Stanley I. Rapoport
Keyword(s):  
Down Syndrome ◽  
Mental Retardation ◽  
Mouse Models ◽  
Trisomy 16
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