Dock7エクソン3および4の欠失は、骨小梁微細構造の低下と石灰化の減少をもたらす

Dedicator of Cytokinesis 7 (DOCK7) has recently emerged as a regulator of skeletal homeostasis, but existing Dock7 mutant models harbor only global mutations and are incompatible with tissue-specific deletion studies. We previously generated a Dock7 -floxed allele in which exons 3-4 are flanked by LoxP sites. To validate the utility of this allele for future conditional strategies, we globally deleted exons 3-4 to generate Dock7 ^em2/em2 mice and characterized their skeletal phenotype. Dock7 ^em2/em2 mice exhibited a diluted coat color and white belly spot, consistent with spontaneous Dock7 mutations. Bone microarchitecture was assessed in 21-week-old males and females. Global deletion of Dock7 exons 3-4 resulted in a 30-37% reduction in trabecular bone volume in the distal femur and L5 vertebrae. Cortical bone thickness was unchanged in both sexes; however, male Dock7 ^em2/em2 mice displayed reduced total femoral area, whereas females showed increased medullary area. These data suggest altered appositional bone growth with mutation of Dock7 . To assess osteoblast function, bone marrow stromal cells (BMSCs) were differentiated in vitro. Dock7 ^em2/em2 BMSCs exhibited reduced mineralization and decreased Bglap expression, indicating attenuated osteoblast differentiation. These findings demonstrate that Dock7 exons 3-4 are required for normal trabecular bone acquisition and osteoblast function. Loss of these exons disrupts DOCK7 activity, supporting the Dock7 ^em2/em2 line as a valid loss-of-function model. The Dock7 ^em2/em2 mouse provides a foundation for future tissue-specific deletion studies to define the cellular roles of DOCK7 in regulating bone formation and trabecular architecture.