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Keywords:

  • animal model;
  • development;
  • mouse;
  • trisomy

Abstract

Many questions related to the development and the phenotypic expression of trisomy (Ts) are amenable to systematic investigation in a mouse model that allows the induction of Ts 1 to 19 by a breeding design of mice heterozygous for Robertsonian metacentric chromosomes. Some Ts do not survive the first critical phase of organogenesis on days 11 to 12 of fetal development; others as Ts 12, 14, 16, 18, and 19, have a life span until or beyond birth. Model type studies of the morphogenesis of developmental anomalies (e.g. craniocerebral, cardiovascular, or placental) are possible in Ts with a longer developmental span, and Ts 16 of the mouse is considered as a natural model of human trisomy 21. The eventual breakdown and death of the trisomic organism are inevitable. There is considerable interest to find ways for rescue and longer survival of Ts in competitive developmental systems, as e.g., in Ts ⟷ 2n blastocyst chimeras, or by isolation of trisomic cellular or tissue systems. Thus, the transfer of Ts hemopoietic stem cells of the fetal liver to irradiated adult recipients is a means of studying the functional capacities and maturation of trisomic hemopoiesis and lymphopoiesis. Both are almost completely restored by Ts 12, 14, 18, and 19 stem cell transplantation with survival periods of more than 6 months. But in other Ts, as of chromosomes 13 or 16, such capacity of reconstitution is impaired. The stepwise analysis of the effects of chromosome triplication on the cell level, in isolated functional systems and in the embryonic organism, is a promising way to understand the phenotypic expression of genome anomalies in complex developmental processes.