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A mouse model for Down syndrome exhibits learning and behaviour deficits
R H Reeves1, N G Irving, T H Moran
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nature Genetics
|October 1, 1995
Summary
Down syndrome (Trisomy 21) is linked to cognitive deficits. Ts65Dn mice, models for Down syndrome, show impaired learning, suggesting gene dosage imbalance contributes to cognitive impairment.
Area of Science:
- Genetics
- Neuroscience
- Developmental Biology
Background:
- Down syndrome (Trisomy 21) is the most common genetic cause of intellectual disability.
- The Ts65Dn mouse model carries a segmental trisomy of mouse chromosome 16, analogous to human chromosome 21q21-22.3, the Down syndrome 'critical region'.
Purpose of the Study:
- To investigate the contribution of gene dosage imbalance in the Down syndrome critical region to cognitive deficits.
- To evaluate the Ts65Dn mouse model for learning and memory impairments relevant to Down syndrome.
Main Methods:
- Behavioral testing of Ts65Dn mice in complex learning tasks requiring visual-spatial integration.
- Analysis of cognitive performance in Ts65Dn mice compared to euploid controls.
Main Results:
- Ts65Dn mice did not exhibit early-onset Alzheimer disease pathology.
- Ts65Dn mice demonstrated significantly impaired performance in a complex learning task.
- The observed learning impairment was reproducible across Ts65Dn mice, suggesting a genetic basis.
Conclusions:
- Dosage imbalance for genes within the Down syndrome critical region contributes to cognitive impairments.
- These findings in Ts65Dn mice may inform our understanding of cognitive deficits in human Down syndrome.