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Characterization of a novel murine Sost ERT2 Cre model targeting osteocytes

Bone Research 2019年第1期7卷 41-53页

作者： delphine B.Maurel Tsutomu Matsumoto Julian A.Vallejo Mark L.Johnson Sarah L.Dallas Yukiko Kitase Marco Brotto Michael J.Wacker Marie A.Harris Stephen E.Harris Lynda F.Bonewald Department of Oral and Craniofacial Sciences University of Missouri-Kansas City School of DentistryKansas CityMOUSA Department of Anatomy and Cell Biology Indiana University School of MedicineIndianapolisINUSA Bone.Muscle Collaborative Sciences College of Nursing and Health InnovationUniversity of Texas at ArlingtonArlingtonUSA Department of Biomedical Sciences University of Missouri-Kansas City School of MedicineKansas CityMOUSA University of Texas Health Science Center San AntonioTXUSA Department of Orthopaedic Surgery Indiana University School of MedicineIndianapolisINUSA Pharmaceutical Sciences Department Universite de BordeauxBio-TisINSERM Unité1026 BioTis146 Rue Léo Saignat33076 BordeauxFrance

Transgenic mice are widely used to delete or overexpress genes in a cell specific manner to advance knowledge of bone biology,function and *** numerous Cre models exist to target gene recombination in osteoblasts and osteoclasts,few target osteocytes specifically,particularly mature *** goal was to create a spatial and temporal conditional Cre model using tamoxifen to induce Cre activity in mature osteocytes using a Bac construct containing the 5’and 3’regions of the Sost gene(Sost ERT2 Cre).Four founder lines were crossed with the Ai9 Cre reporter *** founder line showed high and specific activity in mature *** and organs were imaged and fluorescent signal *** no activity was observed in 2 day old pups,by 2 months of age some osteocytes were positive as osteocyte Cre activity became spontaneous or‘leaky’with *** percentage of positive osteocytes increased following tamoxifen injection,especially in males,with 43%to 95%positive cells compared to 19%to 32%in *** signal was observed in any bone surface cell,bone marrow,nor in muscle with or without tamoxifen *** spontaneous signal was observed in any other ***,with tamoxifen injection,a few positive cells were observed in kidney,eye,lung,heart and *** other organs,28 in total,were negative with tamoxifen ***,with age,a muscle phenotype was apparent in the Sost-ERT2 Cre ***,although this mouse model may be useful for targeting gene deletion or expression to mature osteocytes,the muscle phenotype may restrict the use of this model to specific applications and should be considered when interpreting data.

关键词： cell knowledge model

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