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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  Dmp1-Cre  mouse, expressing Cre from a 14-kb DNA fragment of the mouse  Dmp1  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  Ai9  reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice,  Dmp1-Cre  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,  Dmp1-Cre  marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express  Pdgfra . Confirming the utility of  Dmp1-Cre  in the gastrointestinal mesenchyme, deletion of  Bmpr1a  with  Dmp1-Cre  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  Dmp1-Cre  because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.

Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice