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 abnormalities, 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 alpha (CBFA) is a candidate whose overexpression could affect hematopoietic development. 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 the liver and spleen, whereas the proportion of developing thymocyte populations and that of the erythroid cells in liver and spleen were increased. Furthermore, when analyzing the expression of Cbfa2 in both whole fetuses and isolated thymuses, we found no significant differences in the absolute amount of Cbfa2 mRNA or in the ratio of the isoforms Cbfa2.1 and Cbfa2.2 between Ts16 and diploid samples. Thus, a disequilibrium of Cbfa2 expression and a dysregulation of the two Cbfa2 mRNA species as a cause for the abnormalities in Ts16 fetuses in general and the deficient Ts16 thymocyte development in particular appears unlikely.