Figure 1.

Undecalcified, methyl-methacrylate-embedded transverse histological sections from the midshaft femur of two littermate male mice. The sections are unstained and were imaged under epifluorescent light filtered to excite the oxytetracycline (pale yellow) calcein (green), and alizarin (red) labels that were injected in vivo 8, 6, and 2 weeks before sacrifice, respectively. The mouse in the upper panel is wild-type for Lrp5, whereas the mouse in the lower panel carries a missense mutation in Lrp5 (Arg→Val at amino acid 201, the mouse analog of human amino acid 214) identified in a human family that has HBM. The bone-seeking fluorochrome labels reveal the more rapid and extensive bone modeling activity in the Lrp5 mutant mice (note the extend of both periosteal [gold arrows] and endocortical [red arrows] surface labeling in the mutant), which ultimately leads to a thicker and broader bone cross section in the A214V knockin mice.