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© The Rockefeller University Press, 0021-9525/2002/4/195-b $5.00
The Journal of Cell Biology, Volume 157, Number 2, April 15, 2002 195-b-195

For healthy eyes and bones

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 independent osteogenesis pathway. In addition, Lrp5 knockout mice retain part of the embryonic eye vascularization network, which regresses postnatally in wild-type mice by macrophage- mediated apoptosis. Since normal ocular macrophages are present in the mutant mice, Lrp5 appears to be specifically required for macrophage-mediated apoptosis. The authors are now trying to determine whether other aspects of bone biology are governed by the Lrp5-mediated osteogenesis pathway, and which Wnt proteins signal through this pathway.

Alan W. Dove

alanwdove{at}earthlink.net

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Related Article

Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor

Masaki Kato, Millan S. Patel, Regis Levasseur, Ivan Lobov, Benny H.-J. Chang, Donald A. Glass, II, Christine Hartmann, Lan Li, Tae-Ho Hwang, Cory F. Brayton, Richard A. Lang, Gerard Karsenty, and Lawrence Chan
J. Cell Biol. 2002 157: 303-314. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 186K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?