Aging and intellectual disability: Insights from mouse models of down syndrome

2013 ◽  
Vol 18 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Aarti Ruparelia ◽  
Matthew L. Pearn ◽  
William C. Mobley
Keyword(s):  
Down Syndrome ◽  
Intellectual Disability ◽  
Mouse Models

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 Longitudinal neuroanatomical and behavioral analyses show phenotypic drift and variability in the Ts65Dn mouse model of Down syndrome

2020 ◽  
Vol 13 (9) ◽  
pp. dmm046243 ◽  
Author(s):  
Patricia R. Shaw ◽  
Jenny A. Klein ◽  
Nadine M. Aziz ◽  
Tarik F. Haydar
Keyword(s):  
Down Syndrome ◽  
Intellectual Disability ◽  
Mouse Model ◽  
Mouse Models ◽  
Future Research ◽  
Ts65dn Mouse ◽  
Postnatal Brain ◽  
Comprehensive Comparison ◽  
Underlying Mechanisms ◽  
Phenotypic Drift

ABSTRACTMouse models of Down syndrome (DS) have been invaluable tools for advancing knowledge of the underlying mechanisms of intellectual disability in people with DS. The Ts(1716)65Dn (Ts65Dn) mouse is one of the most commonly used models as it recapitulates many of the phenotypes seen in individuals with DS, including neuroanatomical changes and impaired learning and memory. In this study, we use rigorous metrics to evaluate multiple cohorts of Ts65Dn ranging from 2014 to the present, including a stock of animals recovered from embryos frozen within ten generations after the colony was first created in 2010. Through quantification of prenatal and postnatal brain development and several behavioral tasks, our results provide a comprehensive comparison of Ts65Dn across time and show a significant amount of variability both across cohorts as well as within cohorts. The inconsistent phenotypes in Ts65Dn mice highlight specific cautions and caveats for use of this model. We outline important steps for ensuring responsible use of Ts65Dn in future research.This article has an associated First Person interview with the first author of the paper.

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 Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness, Intellectual Disability, Seizures, and a Down Syndrome-like Facies

2015 ◽  
Vol 96 (5) ◽  
pp. 816-825 ◽  
Author(s):  
Marcello Niceta ◽  
Emilia Stellacci ◽  
Karen W. Gripp ◽  
Giuseppe Zampino ◽  
Maria Kousi ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Intellectual Disability

Animal Models of Down Syndrome

2021 ◽  
Author(s):  
Anna J. Moyer ◽  
Roger H. Reeves
Keyword(s):  
Down Syndrome ◽  
Cognitive Impairment ◽  
Intellectual Disability ◽  
Animal Models ◽  
Brain Regions ◽  
Laboratory Mice ◽  
Tremendous Progress ◽  
New Treatments ◽  
And Function ◽  
Early Developmental

Is intellectual disability a treatable feature of persons with Down syndrome? Researchers have made tremendous progress in the last 30 years, from creating the first mouse model of Down syndrome to completing the first major clinical trial for cognitive impairment in people with Down syndrome. Until recently, normalizing brain development and function seemed too lofty a goal, and indeed, even proposing a candidate therapy requires answering a number of difficult questions. How does trisomy 21, a molecular diagnosis, cause the clinical phenotypes of Down syndrome? When, where, and how do trisomic genes act to disrupt normal development and which genes are involved with which outcomes? Which brain regions and behaviors are most impaired? Is there an early developmental window of time during which treatments are most effective? This article discusses how animal models such as laboratory mice can be used to understand intellectual disability and to develop new treatments for cognitive impairment.

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.

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