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The spatial and temporal pattern of endogenous sFRP1 expression and loss\u2010of\u2010function were examined in the sFRP1\u2010LacZ knock\u2010in mouse (sFRP1<jats:sup>\u2212\/\u2212<\/jats:sup>) during embryonic development and post\u2010natal growth. \u03b2\u2010gal activity representing sFRP1 expression is robust in brain, skeleton, kidney, eye, spleen, abdomen, heart and somites in early embryos, but sFRP1 gene inactivation in these tissues did not compromise normal embryonic and post\u2010natal development. Kidney histology revealed increased numbers of glomeruli in KO mice, observed after 5 years of breeding. In the skeleton, we show sFRP1 expression is found in relation to the mineralizing front of bone tissue during skeletal development from E15.5 to birth. Trabecular bone volume and bone mineral density in the sFRP1<jats:sup>\u2212\/\u2212<\/jats:sup> mouse compared to WT was slightly increased during post\u2010natal growth. Calvarial osteoblasts from newborn sFRP1<jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited a 20% increase in cell proliferation and differentiation at the early stages of osteoblast maturation. sFRP1 expression was observed in osteoclasts, but this did not affect osteoclast number or activity. These findings have identified functions for sFRP1 in kidney and bone that are not redundant with other sFRPs. In summary, the absence of major organ abnormalities, the enhanced bone formation and a normal life span with no detection of spontaneous tumors suggests that targeting sFRP1 can be used as a therapeutic strategy for increasing bone mass in metabolic bone disorders or promoting fracture healing by modulating Wnt signaling. J. Cell. Physiol. 217: 113\u2013126, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21482","type":"journal-article","created":{"date-parts":[[2008,5,22]],"date-time":"2008-05-22T17:16:59Z","timestamp":1211476619000},"page":"113-126","source":"Crossref","is-referenced-by-count":49,"title":["Expression of secreted frizzled related protein 1, a Wnt antagonist, in brain, kidney, and skeleton is dispensable for normal embryonic 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