Value of an animal model for trisomy.

Abstract

Problems related to the developmental pathology of fetal aneuploidy are amenable to systematic investigation in a mouse model of autosomal trisomy. With a breeding design of one parent doubly heterozygous for two partially homologous Robertsonian metacentrics, some of the monosomies and all nineteen trisomies of the mouse can be studied. Monosomies are eliminated either before or shortly after implantation. Some trisomies do not survive a first critical phase of organogenesis on days 11 to 12 of fetal development, others such as Ts 12 to 14, 16, 18, and 19 have a lifespan until or beyond birth. A critical situation of long duration is caused in late development by hypoplasia of the placental labyrinth and ensuing impairment of metabolic exchange and of oxygen supply to the fetus. Model type morphogenetic analyses of anomalies (e.g. cranio-cerebral, cardio-vascular), are possible in Ts 1, 12, 14, 19, and others, and Ts 16 of the mouse is considered to be a close and natural model of human trisomy 21. The eventual breakdown and death of the aneuploid organism is inevitable. However, the introduction of monosomic or the transfer of trisomic haemopoietic stem cells to irradiated recipients is a means of rescuing the aneuploid cells and tissues with longer survival. Under these conditions isolated trisomic haemapoiesis can show almost complete and near-normal maturation, at least in trisomies 12 and 19. In other trisomies (e.g., 13 and 16) stem cell defects impair such reconstitution. The experimental induction of mouse aneuploidy is a powerful technique which allows us to fill gaps in our existing knowledge of human trisomy, and suggests new lines of research. These are the major benefits of an experimental model.