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Sebrie, C ; Chabert, C ; Ledru, A ; Guedj, F ; Po, C ; Smith, DJ ; Rubin, E ; Rivals, I ; Beloeil, JC ; Gillet, B ; Delabar, JM

Increased dosage of DYRK1A and brain volumetric alterations in a YAC model of partial trisomy 21

Anatomical Record-Advances in Integrative Anatomy and Evolutionary Biology 291 (3) 254-262

par Administrateur - publié le

Abstract :

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%).