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Fetal loss in homozygous mutant Norrie disease mice: A new role of Norrin in reproduction
Author(s) -
Luhmann Ulrich F.O.,
Meunier Dominique,
Shi Wei,
Lüttges Angela,
Pfarrer Christiane,
Fundele Reinald,
Berger Wolfgang
Publication year - 2005
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.20141
Subject(s) - biology , allele , genetics , conditional gene knockout , gene , mutant , phenotype
Abstract Mutations in the Norrie disease pseudoglioma gene ( NDP ) are known to cause X‐linked recessive Norrie disease. In addition, NDP mutations have been found in other vasoproliferative retinopathies such as familial exudative vitreoretinopathy, retinopathy of prematurity, and Coats disease, suggesting a role for Norrin in vascular development. Here we report that female mice homozygous for the Norrie disease pseudoglioma homolog ( Ndph ) knockout allele exhibit almost complete infertility, while heterozygous females and hemizygous males are fertile. Histological examinations and RNA in situ hybridization analyses revealed defects in vascular development and decidualization in pregnant Ndph −/− females from embryonic day 7 (E7) onwards, resulting in embryonic loss. Using RT‐PCR analyses we also demonstrate, for the first time, the expression of Ndph in mouse uteri and deciduae as well as the expression of NDP in human placenta. Taken together, these data provide strong evidence for Norrin playing an important role in female reproductive tissues. genesis 42:253–262, 2005. © 2005 Wiley‐Liss, Inc.