Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice

Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel–Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma. The VHL gene was disrupted by targeted homologous recombi...

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Prif Awduron: Gnarra, James R., Ward, Jerrold M., Porter, Forbes D., Wagner, Joseph R., Devor, Deborah E., Grinberg, Alex, Emmert-Buck, Michael R., Westphal, Heiner, Klausner, Richard D., Linehan, W. Marston
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Cyhoeddwyd: National Academy of Sciences 1997
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Biological Sciences
Mynediad Ar-lein:https://ncbi.nlm.nih.gov/pmc/articles/PMC23053/
https://ncbi.nlm.nih.gov/pubmed/9256442
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spelling pubmed-230532001-03-09 Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice Gnarra, James R. Ward, Jerrold M. Porter, Forbes D. Wagner, Joseph R. Devor, Deborah E. Grinberg, Alex Emmert-Buck, Michael R. Westphal, Heiner Klausner, Richard D. Linehan, W. Marston Proc Natl Acad Sci U S A Biological Sciences Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel–Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma. The VHL gene was disrupted by targeted homologous recombination in murine embryonic stem cells, and a mouse line containing an inactivated VHL allele was generated. While heterozygous VHL (+/−) mice appeared phenotypically normal, VHL −/− mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5). Homozygous VHL −/− embryos appeared to develop normally until E9.5 to E10.5, when placental dysgenesis developed. Embryonic vasculogenesis of the placenta failed to occur in VHL −/− mice, and hemorrhagic lesions developed in the placenta. Subsequent hemorrhage in VHL −/− embryos caused necrosis and death. These results indicate that VHL expression is critical for normal extraembryonic vascular development. National Academy of Sciences 1997-08-19 /pmc/articles/PMC23053/ /pubmed/9256442 Text en
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Biological Sciences
spellingShingle Biological Sciences
Gnarra, James R.
Ward, Jerrold M.
Porter, Forbes D.
Wagner, Joseph R.
Devor, Deborah E.
Grinberg, Alex
Emmert-Buck, Michael R.
Westphal, Heiner
Klausner, Richard D.
Linehan, W. Marston
Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
description Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel–Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma. The VHL gene was disrupted by targeted homologous recombination in murine embryonic stem cells, and a mouse line containing an inactivated VHL allele was generated. While heterozygous VHL (+/−) mice appeared phenotypically normal, VHL −/− mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5). Homozygous VHL −/− embryos appeared to develop normally until E9.5 to E10.5, when placental dysgenesis developed. Embryonic vasculogenesis of the placenta failed to occur in VHL −/− mice, and hemorrhagic lesions developed in the placenta. Subsequent hemorrhage in VHL −/− embryos caused necrosis and death. These results indicate that VHL expression is critical for normal extraembryonic vascular development.
author Gnarra, James R.
Ward, Jerrold M.
Porter, Forbes D.
Wagner, Joseph R.
Devor, Deborah E.
Grinberg, Alex
Emmert-Buck, Michael R.
Westphal, Heiner
Klausner, Richard D.
Linehan, W. Marston
author_facet Gnarra, James R.
Ward, Jerrold M.
Porter, Forbes D.
Wagner, Joseph R.
Devor, Deborah E.
Grinberg, Alex
Emmert-Buck, Michael R.
Westphal, Heiner
Klausner, Richard D.
Linehan, W. Marston
author_sort Gnarra, James R.
title Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
title_short Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
title_full Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
title_fullStr Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
title_full_unstemmed Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice
title_sort defective placental vasculogenesis causes embryonic lethality in vhl-deficient mice
publisher National Academy of Sciences
publisher_facet National Academy of Sciences
publishDate 1997
url https://ncbi.nlm.nih.gov/pmc/articles/PMC23053/
https://ncbi.nlm.nih.gov/pubmed/9256442
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