Abstract
Two animal models of Down syndrome (human trisomy 21) with segmental trisomy for all (Ts65Dn) or part (Ts1Cje) of human chromosome 21-homologous region of mouse chromosome 16 have cognitive and behavioral abnormalities. To compare these trisomies directly and to assess the phenotypic contribution of the region of difference between them, Ts65Dn, Ts1Cje, and a new segmental trisomic (Ms1Ts65) for the region of difference (App to Sod1) have been generated as littermates and tested in parallel. Although the performance of Ts1Cje mice in the Morris water maze is similar to that of Ts65Dn mice, the reverse probe tests indicate that Ts65Dn is more severely affected. By contrast, the deficits of Ms1Ts65 mice are significantly less severe than those of Ts65Dn. Therefore, whereas triplication of Sod1 to Mx1 plays the major role in causing the abnormalities of Ts65Dn in the Morris water maze, imbalance of App to Sod1 also contributes to the poor performance. Ts65Dn mice are hyperactive and Ts1Cje mice are hypoactive; the activity of Ms1Ts65 mice is not significantly above normal. These findings indicate that genes in the Ms1Ts65 trisomic region must interact with others in the Ts1Cje region to produce hyperactivity in Ts65Dn mice.
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Abbreviations
- DS:
-
Down syndrome
- MMU 16:
-
mouse chromosome 16
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Acknowledgements
The authors thank R. Gacayan and M. Doan for excellent animal care, A.M. Gillespie for technical assistance, M. Davisson for the original strain of Ts65Dn mice, and P. Bacchetti for statistical analysis.
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This work was supported by grants from the National Institutes of Health (AG08938, HD04024, HD17499, HD31498, and HL18574) and from the Adler Foundation and the McGowan Charitable Trust.
Dr. Charles J. Epstei, Department of Pediatrics, University of California, Box 0748, San Francisco, CA 94143-0748, U.S.A.
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Sago, H., Carlson, E., Smith, D. et al. Genetic Dissection of Region Associated with Behavioral Abnormalities in Mouse Models for Down Syndrome. Pediatr Res 48, 606–613 (2000). https://doi.org/10.1203/00006450-200011000-00009
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DOI: https://doi.org/10.1203/00006450-200011000-00009
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