Unintended targeting ofDmp1-Crereveals 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. TheDmp1-Cremouse, expressing Cre from a 14-kb DNA fragment of the mouseDmp1gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using theAi9reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice,Dmp1-Cretargets 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-Cremarks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that expressPdgfra. Confirming the utility ofDmp1-Crein the gastrointestinal mesenchyme, deletion ofBmpr1awithDmp1-Crecauses numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when usingDmp1-Crebecause it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.
Department of Orthopaedic Surgery, Washington University School of Medicine , St. Louis, MO, USA.
Joohyun
J
Lim
Division of Gastroenterology, Departments of Medicine and Pathology and Immunology, Washington University School of Medicine , St. Louis, MO, USA.
Joseph
J
Burclaff
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA; Department of Orthopedics, The Second Xiangya Hospital, Central South University, Hunan 410011, China.
Guangxu
G
He
Division of Gastroenterology, Departments of Medicine and Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
Jason C
JC
Mills
Department of Orthopaedic Surgery, Washington University School of Medicine, St. Louis, MO, USA; Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.
Fanxin
F
Long