We hypothesize that the trisomy 21 (Down syndrome) is the additive and interactive outcome of the triple copy of different regions of HSA21. Because of the small number of patients with partial trisomy 21, we addressed the question in the Mouse in which three chromosomal regions located on MMU10, MMU17 and MMU16 carries almost all the HSA21 homologs. Male mice from four segmental trisomic strains covering the D21S17-ETS2 (syntenic to MMU16) were examined with an exhaustive battery of cognitive tests, motor tasks and MRI and compared with TS65Dn that encompasses D21S17-ETS2. None of the four strains gather all the impairments (measured by the effect size) of TS65Dn strain. The 152F7 strain was close to TS65Dn for motor behavior and reference memory and the three other strains 230E8, 141G6 and 285E6 for working memory. Episodic memory was impaired only in strain 285E6. The hippocampus and cerebellum reduced sizes that were seen in all the strains indicate that trisomy 21 is not only a hippocampus syndrome but that it results from abnormal interactions between the two structures.
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We thank INSERM U 910 “Génétique Médicale, Génomique Fonctionnelle”, CNRS UMR 7290 Psychologie cognitive, Fédération de Recherche 3C–Comportement Cerveau–Cognition, and Aix Marseille University, and also the Fondation Jérôme Lejeune. AFI-Aveyron provided invaluable assistance with computer software for the MWM analysis and the Cavalieri stereology method. We wish to express our gratitude to the European Mouse Mutant Archive (EMMA) for the generous gift of two strains of segmental trisomic mice. Maire-Laure Dessain (UPS 44 TAAM, CNRS) genotyped the mice. Our special thanks to the anonymous reviewers of the first version of the manuscript and to Doctor Henri Bléhaut for his scientific support.
Conceived and designed the experiments: P-L Roubertoux, M. Carlier, S. Tordjman. Behavioral assessment of the mice: P-L Roubertoux, A. Ghata, C. Bartoli, M. Carlier. MRI: N Baril. P. Cau, P-L. Roubertoux. Data analysis : P-L Roubertoux, M Carlier. Molecular analysis: J. di Christofaro, P Bourgeois, P-L Roubertoux. Mouse breeding: C. Scajola. Wrote the paper: P-L Roubertoux, M Carlier. All the authors reviewed the manuscript for intellectual content and approved submission.
Conflict of interest
Pierre L. Roubertoux, Nathalie Baril, Pierre Cau, Christophe Scajola, Adeline Ghata, Catherine Bartoli, Patrice Bourgeois, Julie di Christofaro, Sylvie Tordjman, Michèle Carlier declare that they have no conflict of interests.
The protocols for the present study were approved by the Comité d’éthique pour l’expérimentation animale n°14, under the title “Rôle de la région D21517-ET52 (MMU 16) dans les dysfonctions cérébrales de souris modèles du syndrome de Down,” with PL Roubertoux as the main investigator (reference number 23- 23092012, dated October 11, 2012).
Edited by Stephen Maxson.
An erratum to this article is available at http://dx.doi.org/10.1007/s10519-017-9845-3.
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Roubertoux, P.L., Baril, N., Cau, P. et al. Differential Brain, Cognitive and Motor Profiles Associated with Partial Trisomy. Modeling Down Syndrome in Mice. Behav Genet 47, 305–322 (2017). https://doi.org/10.1007/s10519-017-9835-5
- Trisomy 21
- D21S17-ETS2 region
- Protein–protein interactions
- Effect size