Jean Maurice Delabar

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.

Aneuploidies have diverse phenotypic consequences, ranging from mental retardation and developmental abnormalities to susceptibility to common phenotypes and various neoplasms. This review focuses on the developmental defects of murine models of a prototype human aneuploidy: trisomy 21 (Down syndrome, DS, T21). Murine models are clearly the best tool for dissecting the phenotypic consequences of imbalances that affect single genes or chromosome segments. Embryos can be studied freely in mice, making murine models particularly useful for the characterization of developmental abnormalities. This review describes the main phenotypic alterations occurring during the development of patients with T21 and the developmental abnormalities observed in mouse models, and investigates phenotypes common to both species.