Mouse chimeras composed of trisomy 16 and normal (2N) cells: preliminary studies

Many humans with trisomy 21 (Down Syndrome (DS)) have psychomotor and cognitive retardation, congenital heart disease, and hematologic abnormalities. Partial genetic homology exists between mouse chromosome 16 and human chromosome 21; thus, studies of the development of mice with trisomy 16 (Ts16) may provide important insights into the pathogenesis of these defects and into the mechanisms by which they arise in humans. Since Ts16 mice do not survive the late fetal period, chimeras have been formed between Ts16 and normal (2N) mouse embryos to rescue the Ts16 cells for postnatal studies. In this preliminary study of the postnatal development of such chimeras, we examined the proportion of Ts16 cells in a variety of tissues, including the coat, blood, placenta, heart, and brain. The Ts16 cells made significant contributions to almost all tissues examined. Aspects of the behavior and the neurochemistry of adult Ts16 less than-greater than 2N chimeras were found to differ significantly from control (2N less than-greater than 2N) chimeras and from animals of the two donor embryo strains. Ts16 cells comprised a substantial, but not predominant, proportion of cells in each brain region examined. Suggestions for definitive analyses are reviewed.