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Lrp5 and Lrp6 play compensatory roles in mouse intestinal development
Author(s) -
Zhong Zhendong,
Baker Jacob J.,
ZylstraDiegel Cassandra R.,
Williams Bart O.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23324
Subject(s) - wnt signaling pathway , biology , villin , lrp5 , lrp6 , intestinal epithelium , microbiology and biotechnology , cellular differentiation , signal transduction , epithelium , genetics , gene , actin
Low‐density lipoprotein receptor‐related proteins 5 and 6 (Lrp5 and Lrp6) are co‐receptors of Wnt ligands and play important roles in Wnt/β‐catenin signal transduction. Mice homozygous for a germline deletion of Lrp6 die at birth with several associated defects, while Lrp5‐deficient mice are viable. Here, we conditionally deleted Lrp5 and/or Lrp6 in the mouse gut ( gut−/− ) by crossing mice carrying floxed alleles of Lrp5 and Lrp6 to a strain expressing Cre recombinase from the villin promoter (villin‐ Cre ). The changes in morphology, differentiation, and Wnt signal transduction were validated using immunohistochemistry and other staining. Consistent with observations in mice carrying a homozygous germline deletion in Lrp5, intestinal development in Lrp5 gut −/− mice was normal. In addition, mice homozygous for villin‐ Cre ‐induced deletion of Lrp6 ( Lrp6 gut −/− ) were viable with apparently normal intestinal differentiation and function. However, mice homozygous for villin‐ Cre inactivated alleles of both genes ( Lrp5 gut −/− ; Lrp6 gut −/− ) died within 1 day of birth. Analysis of embryonic Lrp5 gut −/− ; Lrp6 gut −/− intestinal epithelium showed a progressive loss of cells, an absence of proliferation, and a premature differentiation of crypt stem/precursor cells; no notable change in differentiation was observed in the embryos lacking either gene alone. Further immunohistochemical studies showed that expression of the Wnt/β‐catenin target, cyclin D1, was specifically reduced in the intestinal epithelium of Lrp5 gut −/− ; Lrp6 gut −/− embryos. Our data demonstrate that Lrp5 and Lrp6 play redundant roles in intestinal epithelium development, and that Lrp5/6 might regulate intestinal stem/precursor cell maintenance by regulating Wnt/β‐catenin signaling. J. Cell. Biochem. 113: 31–38, 2012. © 2011 Wiley Periodicals, Inc.