Unintended targeting of reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice.

Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The mouse, expressing Cre from a 14-kb DNA fragment of the mouse gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express . Confirming the utility of in the gastrointestinal mesenchyme, deletion of with causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.