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unintended targeting of dmp1-cre reveals a critical role for bmpr1a signaling in the gastrointestinal mesenchyme of adult mice

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Bone Research 2017年第1期5卷 41-48页

作者： Joohyun Lim Joseph Burclaff Guangxu He Jason C Mills Fanxin Long Department of Orthopaedic Surgery Washington University School of MedicineSt.LouisMOUSA Division of Gastroenterology Departments of Medicine and Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA Department of Orthopedics The Second Xiangya HospitalCentral South UniversityHunan 410011China Department of Developmental Biology Washington University School of MedicineSt.LouisMOUSA

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 dmpl- cre mouse, expressing cre from a 14-kb DNA fragment of the mouse dmpl 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, dmpl-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, dmpl-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 dmpl-cre in the gastrointestinal mesenchyme, deletion of bmprla with dmpl-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 dmpl-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.

关键词： gene cell bone unintended targeting of dmp1-cre reveals a critical role for bmpr1a signaling in the gastrointestinal mesenchyme of adult mice Figure

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