Research from University of Miami Miller School of Medicine, Miami, and Beijing Institute of Genomics, China demonstrate, by using Asxl1-targeted mouse models, a crucial role of ASXL1 in the maintenance of Bone marrow stromal cells (BMSCs) functions and skeletal development. The heterogeneous novo mutation of the ASXL1 gene causes Bohring-Opitz syndrome (BOS), a rare congenital disorder.
Asxl1 global loss as well as conditional deletion in osteoblasts [a group of connected cells that synthesize bone] and their progenitors led to significant bone loss and a markedly decreased number of bone marrow stromal cells (BMSCs). Significant delays in growth, reduction of bone mineral density (BMD) and distal femurs as well as reduction of skull size were found in Asxl1-/- mice which reminds microcephaly, IUGR and short stature in patients with BOS. Furthermore, hypoplastic supraorbital ridges, a feature of BOS, were observed.
Another important result of this study is, that the re-introduction of Asxl1 into Asxl1-/- BMSCs restored BMSC self-renewal and lineage commitment.
Bohring-Opitz Syndrome 