Effect of deletion of Impdh2 on gene expression in the forlimbs from E12.5 embryos and osteoclasts (OCs)

Many factors are essential for skeletal development and homeostaisis. Here we report that inosine monophosphate dehydrogenase type II (Impdh2) is a key positive regulator for limb development and bone resorption. Deletion of Impdh2 in limb mesenchymal progenitors impaired the differentiation of mesenchymal cells into chondrocyte. Meanwhile, deletion of Impdh2 in osteoclast precursors results in mice an osteopetrotic phenotype via suppressing osteoclast differentiation. Our results reveal a previously unrecognized role of Impdh2 on skeletal development and homeostasis. Overall design: To investigate the physiological significance and function of Impdh2 in the regulation of limb development and osteoclastogenesis, we respectively generated limb mesenchymal progenitors and myeloid lineage cells, i.e., osteoclast precursors specific Impdh2 knockout mice (Prx-cKO and LysM-cKO mice). We then performed gene expression profiling analysis using data obtained from RNA-seq from forelimbs of Impdh2 WT and Prx-cKO mice embryos at E12.5, and osteoclasts of Impdh2 WT and LysM-cKO mice.