Megakaryocyte-restricted expression of the Cre recombinase.

doi:10.1160/TH11-03-0150 Thromb Haemost 2011; 106: 554 Dear Sirs, In the recently published work from Adam Nowakowski et al. “Megakaryocyte gene targeting mediated by restricted expression of recombinase Cre” (Thromb Haemost 2011; 105.1) the authors present a transgenic mouse strain that allows Cre expression under the control of the alphaIIb promoter (1). Nowakowski et al. (1) suggest that this mouse strain offers megakaryocytes-restricted expression of the Cre recombinase. However, results still raise two significant concerns: (i) In livers of 14.5 dpc (days post conception) fetuses from malphaIIb-cre/ ROSA26 –lacZ mice positive X-Gal staining, which indicates Cre activity, was found in haematopoietic islands. But data are missing which show that these X-Gal positive cells are all megakaryocytes and not also haematopoietic progenitors, such as alphaIIb+ c-kit+ fetal liver cells, which are suggested to contain myeloid progenitors, erythroid progenitors and lymphoid progenitors (2). (ii) Similar is true for X-Gal staining of bone marrow smears from malphaIIb-cre/ROSA26 –lacZ mice. It is indeed possible that these cells represent haematopoietic progenitors as might be concluded from what was previously reported by Tropel et al. (3) and Corbel et al. (2). Tropel et al. (3) suggest that haematopoietic progenitors from bone marrow in which the alphaIIb promotor is active, give rise to CFU-GEMM (colony forming unit – granulocyte, erythrocyte, monocyte, and megakaryocyte) and CFU-mix. Corbel et al. (2) provide evidence that alphaIIb is expressed by bone marrow progenitors belonging to the myeloid, erythroid and T lymphoid lineages. Taken together, further work might be needed to assess whether the Cre-recombinase in the alphaIIb-Cre mouse strain provided by Nowakowski et al. (1) is indeed expressed and active exclusively in the megakaryocytic lineage. Therefore, whether the mouse strain of Nowakowski provides any advantage compared to the alphaIIb-Cre line introduced by Emambokus and Frampton in 2003 (4) has to be shown in future studies.