Increased Dosage of DYRK1A and Brain Volumetric Alterations in a YAC Model of Partial Trisomy 21.

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Sebrié, Catherine | Chabert, Caroline | Ledru, Aurélie | Guedj, Fayçal | Po, Chrystelle | Smith, Desmond J | Rubin, Edward | Rivals, Isabelle | Beloeil, Jean-Claude | Gillet, Brigitte | Delabar, Jean-Maurice

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International audience. A yeast artificial chromosome (YAC) transgenic murine model of partial trisomy 21 overexpressing five human genes-including DYRK1A, which encodes a serine threonine kinase involved in cell cycle control-has been shown to present an increase in brain weight. We analyzed this new phenotype by measuring total and regional brain volumes at different ages, using a 7 Tesla magnetic resonance imaging volumetric approach. Volumetric measurements showed a total volume increase of 13.6% in adult mice. Changes in brain morphogenesis were already visible at a very early postnatal stage (postnatal days 2-7). Region-specific changes were characterized from postnatal day 15 to 5 months. These results, made it possible to define region-specific effects of DYRK1A overexpression, with the strongest increase seen in the thalamus-hypothalamus area (24%). Anat Rec, 291:254-262, 2008. (c) 2008 Wiley-Liss, Inc.

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