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Segmental trisomy as a mouse model for Down syndrome
M T Davisson1, C Schmidt, R H Reeves
1Jackson Laboratory, Bar Harbor, Maine 04609.
Abstract:
Mice trisomic for Chromosome (Chr) 16 have been used extensively as an animal model for human Down Syndrome (Trisomy 21). This system has drawbacks, however: trisomy for all of Chr 16 is incompatible with postnatal survival and produces trisomy for many more genes than those conserved in human Chr 21. We report here the development and preliminary characterization of mice that are trisomic for only the segment of mouse Chr 16 that is conserved in human Chr 21. While these segmentally trisomic mice, Ts(17(16)) 65Dn, do not appear to have all the features characteristic of Down Syndrome, they represent a mouse model that survives to adulthood and may be useful to study features of Down Syndrome that develop later in life, such as susceptibility to infection, increased incidence of leukemia, and Alzheimer-like neuropathology.
Insights
Researchers developed segmentally trisomic mice for a specific region of mouse Chr 16, creating a viable Down Syndrome (Trisomy 21) model. This new model allows adult study of late-onset Down Syndrome features.
Area of Science:
- Genetics
- Developmental Biology
- Animal Models
Background:
- Mice trisomic for entire Chromosome (Chr) 16 serve as a model for human Down Syndrome (Trisomy 21).
- Existing Chr 16 trisomic mouse models have limitations, including incompatibility with postnatal survival and trisomy for numerous non-conserved genes.
- This necessitates improved animal models for studying Down Syndrome.
Purpose of the Study:
- To develop and characterize a novel mouse model trisomic for a specific segment of mouse Chr 16.
- This segment is conserved in human Chr 21, aiming for a more accurate Down Syndrome model.
- To assess the viability and potential utility of this segmentally trisomic model for Down Syndrome research.
Main Methods:
- Development of segmentally trisomic mice, designated Ts(17(16)) 65Dn.
- These mice carry trisomy for a defined chromosomal segment homologous to human Chr 21.
- Preliminary characterization of the Ts(17(16)) 65Dn mouse model.
Main Results:
- Successful development of segmentally trisomic mice (Ts(17(16)) 65Dn) that survive to adulthood.
- These mice exhibit trisomy for a specific Chr 16 segment conserved with human Chr 21.
- The model does not fully replicate all Down Syndrome features but offers a viable alternative.
Conclusions:
- Segmentally trisomic mice Ts(17(16)) 65Dn provide a viable adult model for Down Syndrome research.
- This model may be instrumental in studying late-onset Down Syndrome phenotypes.
- Potential applications include research into infection susceptibility, leukemia incidence, and Alzheimer-like neuropathology in Down Syndrome.