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

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 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

scholarly journals The Use of Mouse Models for Understanding the Biology of Down Syndrome and Aging

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Guido N. Vacano ◽  
Nathan Duval ◽  
David Patterson
Keyword(s):  
Down Syndrome ◽  
Human Chromosome ◽  
Mouse Models ◽  
Targeted Mutagenesis ◽  
Chromosome 21 ◽  
Practical Reasons ◽  
Future Directions ◽  
Human Chromosome 21 ◽  
Biology Of Aging ◽  
Chromosome Regions

Down syndrome is a complex condition caused by trisomy of human chromosome 21. The biology of aging may be different in individuals with Down syndrome; this is not well understood in any organism. Because of its complexity, many aspects of Down syndrome must be studied either in humans or in animal models. Studies in humans are essential but are limited for ethical and practical reasons. Fortunately, genetically altered mice can serve as extremely useful models of Down syndrome, and progress in their production and analysis has been remarkable. Here, we describe various mouse models that have been used to study Down syndrome. We focus on segmental trisomies of mouse chromosome regions syntenic to human chromosome 21, mice in which individual genes have been introduced, or mice in which genes have been silenced by targeted mutagenesis. We selected a limited number of genes for which considerable evidence links them to aspects of Down syndrome, and about which much is known regarding their function. We focused on genes important for brain and cognitive function, and for the altered cancer spectrum seen in individuals with Down syndrome. We conclude with observations on the usefulness of mouse models and speculation on future directions.

First-in-human clinical trial with intratumoral BO-112 in solid malignancies: A novel immunotherapy based in double-stranded RNA (dsRNA).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3082-3082 ◽  
Author(s):  
Ivan Marquez Rodas ◽  
Maria E. Rodriguez-Ruiz ◽  
Sara Lopez-Tarruella ◽  
Jose Luis Perez-Gracia ◽  
Enrique de Miguel ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mouse Models ◽  
Immune Cells ◽  
Biological Effects ◽  
Safety Data ◽  
Metastatic Lesion ◽  
Post Treatment ◽  
It Use ◽  
Antitumor Effects ◽  
Solid Malignancies

3082 Background: BO-112 is a double stranded synthetic RNA, formulated with the cationic carrier polyethyleneimine that preclinically improves its intracellular delivery and resistance towards nuclease degradation. In melanoma mouse models, systemic administration activates MDA-5 and NOXA, leading to anti-tumoral activity connected to a sustained and extended expression of IFN-response genes. Intratumoral (IT) delivery, seeking a safer and more focused enhancement of local and systemic antitumor effects has been tested in transplanted mouse models. The potential of its IT use as an immune-modulatory treatment, as well as its toxicity profile, is being analyzed in this first in human, proof of concept, clinical trial (NCT02828098). Methods: Four patients with malignant solid tumors and palpable cutaneous/subcutaneous or lymph node metastases >1 cm were treated with a single BO-112 dose of 0.6 mg/ml IT. Pre and post treatment biopsies from the injected metastatic lesion were obtained. Pharmacokinetics, serum cytokines and circulating immune cells were sequentially studied in pre and post treatment samples. Results: Patients did not experience relevant toxicity with the exception of a single episode of completely reversible grade 4 thrombocytopenia in one patient, attributed to the drug. BO-112 was not detectable in bloodstream following IT delivery. No changes in circulating cytokines were detected. Main immunobiological effects are summarized in the table. Conclusions: BO-112 has shown changes in tumoral immune cells in 1/4 patients, while in 3/4 induced both necrosis and changes in circulating immune cells. This ongoing trial will compile more safety data with repeated sequential administrations, escalated to higher doses of BO-112, and will thoroughly characterize its biological effects in humans with solid malignancies amenable to IT injection. Clinical trial information: NCT02828098. [Table: see text]

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