Mice lacking Lrp5 (right) have low bone mass in their vertebrae.

The Wnt family of secreted proteins controls several crucial developmental processes, some of which are apparently mediated by Wnt coreceptors from the LDL receptor-related protein (Lrp) family. Now, on page 303, Kato et al. report that the targeted disruption of Lrp5 in mice causes a phenotype virtually identical to that seen in humans with osteoporosis-pseudoglioma syndrome. In addition to identifying a long-sought genetic component for bone mass determination, the work identifies Lrp5 as a critical component for controlling both osteogenesis and eye vascularization during late stages of development.Mice lacking functional Lrp5 exhibit lower rates of bone formation than wild-type mice, and fail to achieve normal bone mass early in life. This happens despite normal expression of Cbfa1, a protein thought to be the principal controller of osteogenesis, suggesting that Lrp5 functions in an...

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