Hematopoietic deficiencies and core binding factor expression in murine Ts16, an animal model for Down syndrome

Patients with Down syndrome (DS, Trisomy 21) suffer from hematopoietic abno rmalities, including an increased risk to develop leukemia. Overexpression of chromosome 21-encoded genes thus leads to hematopoietic deficiencies. Of the genes found within the DS chromosomal region, core binding factor alph a (CBFA) is a candidate whose overexpression could affect hematopoietic dev elopment. To learn more about the pathogenesis of hematological diseases in DS, we studied hematopoietic precursor cells in Ts16 mice, an animal model for DS. We found reduced proportions of B lymphoid and myeloid cells in th e liver and spleen, whereas the proportion of developing thymocyte populati ons and that of-the erythroid cells in liver and spleen were increased. Fur thermore, when analyzing the expression of Cbfa2 in both whole fetuses and isolated thymuses, we found no significant differences in the absolute amou nt of Cbfa2 mRNA or in the ratio of the isoforms Cbfa2.1 and Cbfa2.2 betwee n Ts16 and diploid samples. Thus, a disequilibrium of Cbfa2 expression and a dysregulation of the two Cbfa2 mRNA species as a cause for the abnormalit ies in Ts16 fetuses in general and the deficient Ts16 thymocyte development in particular appears unlikely. (C) 1999 Academic Press.