TY - JOUR
T1 - Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice
AU - Lim, Joohyun
AU - Burclaff, Joseph
AU - He, Guangxu
AU - Mills, Jason C.
AU - Long, Fanxin
N1 - Funding Information:
This work is supported by NIH grants AR060456 and AR055923 (FL). JCM is supported by NIH DK105129, DK094989, by DK052574 to the Washington University Digestive Core Centers (DDRCC) and by the pre-Program Project Award from the Siteman Cancer Center Investment Program. JB is supported by the NIGMS cell and Molecular Biology Training Grant (GM007067). Confocal microscopy was supported by the NIH funded George O'Brien Center for Kidney Disease Research (P30DK079333), Kidney translational Research Core and the Renal Division at the Washington University School of Medicine. We thank Masato Hoshi of the Sanjay Jain laboratory for technical assistance with the confocal microscope. Histology imaging was supported by the Alafi Neuroimaging Laboratory, the Hope Center for Neurological Disorders, and NIH Shared Instrumentation Grant (S10 RR0227552) to Washington University.
Publisher Copyright:
© The Author(s) 2017.
PY - 2017/1/31
Y1 - 2017/1/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85011306014&partnerID=8YFLogxK
U2 - 10.1038/boneres.2016.49
DO - 10.1038/boneres.2016.49
M3 - Article
C2 - 28163952
AN - SCOPUS:85011306014
SN - 2095-4700
VL - 5
JO - Bone Research
JF - Bone Research
M1 - 16049
ER -