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Researchers created a Dock7-floxed allele with exons 3–4 flanked by LoxP sites, then globally deleted exons 3–4 to produce Dock7em2/em2 mice. In 21-week-old males and females, trabecular bone volume in distal femur and L5 vertebrae decreased by 30–37%, while cortical thickness stayed unchanged. Dock7em2/em2 bone marrow stromal cells showed reduced mineralization and diminished Bglap expression, indicating impaired osteoblast differentiation. These results establish exons 3–4 as required for normal trabecular bone acquisition and osteoblast function and support Dock7em2/em2 as a valid loss-of-function foundation for future tissue-specific studies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/deletion-of-dock7-exons-3-and-4-results-in-reduced-trabecular-microarchitecture-and-a-decrease-in-mineralization/440612/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/deletion-of-dock7-exons-3-and-4-results-in-reduced-trabecular-microarchitecture-and-a-decrease-in-mineralization/440612.png","ImageObject",300,407,{"name":92,"@type":93},"CatatanPagi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-30","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What genetic change was introduced to study DOCK7 function?","Question",{"text":112,"@type":113},"Exons 3–4 of Dock7 were flanked by LoxP sites in a floxed allele, and then exons 3–4 were globally deleted to generate Dock7em2/em2 mice.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the Dock7 exons 3–4 deletion affect bone microarchitecture?",{"text":117,"@type":113},"Global deletion of Dock7 exons 3–4 produced a 30–37% reduction in trabecular bone volume in the distal femur and L5 vertebrae, while cortical bone thickness was unchanged.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence shows altered osteoblast function in Dock7em2/em2 mice?",{"text":121,"@type":113},"Bone marrow stromal cells differentiated in vitro exhibited reduced mineralization and decreased Bglap expression, indicating attenuated osteoblast differentiation.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},440612,1790779785,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090894170,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","bioRxiv preprint doi: [https://doi.org/10.64898/2025.12.31.696872](https://doi.org/10.64898/2025.12.31.696872); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC 4.0 International license.  \n1 Deletion of Dock7 Exons 3 and 4 Results in Reduced Trabecular Microarchitecture and a  \n2 Decrease in Mineralization  \n3  \n4 Talia Lizottea , Conner Lajoieb , Sarah Portera , Sydney Langc , Felix A. Vespera , Daniel J. Brooksd ,  \n5 Carlos Gartnere , Matthew S. Alexanderf, Calvin Varye , Mary L. Bouxseinc , Kathleen A. Beckerae  \n6  \n7 a Department of Biomedical Sciences, College of Osteopathic Medicine, University of New  \n8 England, Biddeford, ME 04005, USA  \n9 b College of Osteopathic Medicine, University of New England, Biddeford, ME 04005, USA  \n10 c College of Arts and Sciences, University of New England, Biddeford, ME 04005, USA  \n11 d Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA  \n12 e Center for Molecular Medicine, MaineHealth Institute for Research, Scarborough, ME 04074,  \n13 USA  \n14 f University of Alabama at Birmingham Heersink School of Medicine and Children’s of Alabama, 15 Department of Pediatrics, Division of Neurology, Birmingham, AL, USA 35294  \n16 Corresponding author:  \n17 Kathleen Becker, Ph. D.  \n18 College of Osteopathic Medicine  \n19 Department of Biomedical Sciences  \n20 11 Hills Beach Rd  \n21 Biddeford, ME 04005  \n22 Tel (207) 602-2824  \n23  [kbecker3@une.edu](kbecker3@une.edu)  \n24  \n25 Keywords: Dock7, osteoblast, bone, trabecular bone, Bglap  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.31.696872](https://doi.org/10.64898/2025.12.31.696872); this version posted January 2, 2026. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made  \navailable under aCC-BY-NC 4.0 International license.  \n27 Abstract  \n28 Dedicator of Cytokinesis 7 (DOCK7) has recently emerged as a regulator of skeletal  \n29 homeostasis, but existing Dock7 mutant models harbor only global mutations and are  \n30 incompatible with tissue-specific deletion studies. We previously generated a Dock7-floxed  \n31 allele in which exons 3–4 are flanked by LoxP sites. To validate the utility of this allele for future  \n32 conditional strategies, we globally deleted exons 3–4 to generate Dock7em2/em2 mice and  \n33 characterized their skeletal phenotype. Dock7em2/em2 mice exhibited a diluted coat color and  \n34 white belly spot, consistent with spontaneous Dock7 mutations. Bone microarchitecture was  \n35 assessed in 21-week-old males and females. Global deletion of Dock7 exons 3–4 resulted in a  \n36 30–37% reduction in trabecular bone volume in the distal femur and L5 vertebrae. Cortical bone  \n37 thickness was unchanged in both sexes; however, male Dock7em2/em2 mice displayed reduced  \n38 total femoral area, whereas females showed increased medullary area. These data suggest  \n39 altered appositional bone growth with mutation of Dock7. To assess osteoblast function, bone  \n40 marrow stromal cells (BMSCs) were differentiated in vitro. Dock7em2/em2 BMSCs exhibited  \n41 reduced mineralization and decreased Bglap expression, indicating attenuated osteoblast  \n42 differentiation. These findings demonstrate that Dock7 exons 3–4 are required for normal  \n43 trabecular bone acquisition and osteoblast function. Loss of these exons disrupts DOCK7  \n44 activity, supporting the Dock7em2/em2 line as a valid loss-of-function model. The Dock7em2/em2  \n45 mouse provides a foundation for future tissue-specific deletion studies to define the cellular  \n46 roles of DOCK7 in regulating bone formation and trabecular architecture.  \n47  \nbioRxiv preprint doi: [https://doi.org/10.64898/2025.12.31.696","cbCaib0PKMnIDwkU","https://ap.wps.com/l/cbCaib0PKMnIDwkU","pdf",3143635,33,"English","# Abstract\n# Introduction","[{\"question\":\"What genetic change was introduced to study DOCK7 function?\",\"answer\":\"Exons 3–4 of Dock7 were flanked by LoxP sites in a floxed allele, and then exons 3–4 were globally deleted to generate Dock7em2/em2 mice.\"},{\"question\":\"How did the Dock7 exons 3–4 deletion affect bone microarchitecture?\",\"answer\":\"Global deletion of Dock7 exons 3–4 produced a 30–37% reduction in trabecular bone volume in the distal femur and L5 vertebrae, while cortical bone thickness was unchanged.\"},{\"question\":\"What evidence shows altered osteoblast function in Dock7em2/em2 mice?\",\"answer\":\"Bone marrow stromal cells differentiated in vitro exhibited reduced mineralization and decreased Bglap expression, indicating attenuated osteoblast differentiation.\"}]","Deletion of Dock7 Exons 3 and 4 - Results in Reduced Trabecular Microarchitecture and a Decrease in Mineralization | PDF",1790692677,83]