title: Fetal loss in homozygous mutant Norrie disease mice: a new role of Norrin in reproduction.
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.
authors: Division of Medical Molecular Genetics & Gene Diagnostics, Institute of Medical Genetics, University of Zurich, Schwerzenbach, Switzerland.
authors: Ulrich F O
authors: UF
authors: Luhmann
authors: Dominique
authors: D
authors: Meunier
authors: Wei
authors: W
authors: Shi
authors: Angela
authors: A
authors: Lüttges
authors: Christiane
authors: C
authors: Pfarrer
authors: Reinald
authors: R
authors: Fundele
authors: Wolfgang
authors: W
authors: Berger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003638:Deafness / Q000235:genetics; D004195:Disease Models, Animal; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005298:Fertility / Q000235:genetics; D005313:Fetal Death / Q000235:genetics*; D015870:Gene Expression; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D017403:In Situ Hybridization; D007247:Infertility, Female / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D011247:Pregnancy; D012098:Reproduction / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts
chemical_list: D005136:Eye Proteins; C489916:Ndph protein, mouse; D009419:Nerve Tissue Proteins