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.

scholarly journals Adaptation of the Arizona Cognitive Task Battery for use with the Ts65Dn Mouse Model (Mus musculus) of Down syndrome

2016 ◽  
Author(s):  
Michael R. Hunsaker ◽  
Genevieve K. Smith ◽  
Raymond P. Kesner
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Mouse Models ◽  
Cognitive Task ◽  
Novelty Detection ◽  
Visual Object ◽  
Long Term Memory ◽  
Human Populations ◽  
Clinical Neurology ◽  
Ts65dn Mouse

AbstractWe propose and validate a clear strategy to efficiently and comprehensively characterize neurobehavioral deficits in the Ts65Dn mouse model of Down syndrome. This novel approach uses neurocognitive theory to design and select behavioral tasks that test specific hypotheses concerning the results of Down syndrome. In this manuscript we model in Ts65Dn mice the Arizona Cognitive Task Battery used to study human populations with Down syndrome. We observed specific deficits for spatial memory, impaired long-term memory for visual objects, acquisition and reversal of motor responses, reduced motor dexterity, and impaired adaptive function as measured by nesting and anxiety tasks. The Ts65Dn mice showed intact temporal ordering, novelty detection, and visual object recognition with short delays. These results phenocopy the performance of participants with Down syndrome on the Arizona Cognitive Task Battery. This approach extends the utility of mouse models of Down syndrome by integrating the expertise of clinical neurology and cognitive neuroscience into the mouse behavioral laboratory. Further, by directly emphasizing the reciprocal translation of research between human disease states and the associated mouse models, we demonstrate that it is possible for both groups to mutually inform each others’ research to more efficiently generate hypotheses and elucidate treatment strategies.

Memantine Normalizes Several Phenotypic Features in the Ts65Dn Mouse Model of Down Syndrome

2010 ◽  
Vol 21 (1) ◽  
pp. 277-290 ◽  
Author(s):  
Noemí Rueda ◽  
María Llorens-Martín ◽  
Jesús Flórez ◽  
Elsa Valdizán ◽  
Pradeep Banerjee ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Ts65dn Mouse ◽  
Phenotypic Features

Hypothermic responses to 8-OH-DPAT in the Ts65Dn mouse model of Down syndrome

Neuroreport ◽  
2006 ◽  
Vol 17 (8) ◽  
pp. 837-841 ◽  
Author(s):  
Melissa R. Stasko ◽  
Jonah J. Scott-McKean ◽  
Alberto C.S. Costa
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Ts65dn Mouse

P1-049: Chronic Memantine administration reduces APP expression, normalizes glutamatergic synapse density, and improves spatial learning in the Ts65Dn mouse model for down syndrome

2008 ◽  
Vol 4 ◽  
pp. T220-T220
Author(s):  
Carmen Martı́nez-Cué ◽  
Noemı́ Rueda ◽  
Marı́a Llorens-Martı́n ◽  
Jesús Flórez ◽  
Elsa Valdizán ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Spatial Learning ◽  
Glutamatergic Synapse ◽  
Ts65dn Mouse ◽  
Synapse Density
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