Loss of G6b-B results in defective TPO signaling and blocks megakaryocyte-lineage differentiation

We report on a severe macrothrombocytopenia in C57BL/6 mice bearing a spontaneous intronic mutation within Mpig6b resulting in complete loss of G6b-B protein expression. In addition to the myelofibrosis described in G6b-B-deficient mice, Mpig6bmut mice displayed sex-specific differences in platelet reactivity and BM morphology including a dramatic osteosclerosis especially present in females. RNA sequencing of native BM MKs revealed markedly reduced levels of all MK-specific transcripts. mRNA profiles of native bone marrow derived megakaryocytes sequenced on the NextSeq-500 platform with ~30 million reads per sample in single-end mode with 75 nt read length