Vascular Abnormalities and Deregulation of VEGF in Lkb1 -Deficient Mice
Copyright policy )Vascular Abnormalities and Deregulation of VEGF in Lkb1 -Deficient Mice
The LKB1 tumor suppressor gene, mutated in Peutz-Jeghers syndrome, encodes a serine/threonine kinase of unknown function. Here we show that mice with a targeted disruption of Lkb1 die at midgestation, with the embryos showing neural tube defects, mesenchymal cell death, and vascular abnormalities. Extraembryonic development was also severely affected; the mutant placentas exhibited defective labyrinth layer development and the fetal vessels failed to invade the placenta. These phenotypes were associated with tissue-specific deregulation of vascular endothelial growth factor ( VEGF ) expression, including a marked increase in the amount of VEGF messenger RNA. Moreover, VEGF production in cultured Lkb1 −/− fibroblasts was elevated in both normoxic and hypoxic conditions. These findings place Lkb1 in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb1 loss are mediated at least in part by VEGF.
- University of Bergen Norway
- Helsinki University Hospital Finland
- University of Helsinki Finland
- The University of Texas Southwestern Medical Center United States
Lymphokines, Cell Death, Gene Expression Regulation, Developmental, Endothelial Growth Factors, AMP-Activated Protein Kinases, Embryo, Mammalian, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, DNA-Binding Proteins, Mesoderm, Mice, Inbred C57BL, Embryonic and Fetal Development, Mice, Gene Targeting, Animals, Blood Vessels, Endothelium, Vascular, Hypoxia-Inducible Factor 1, Cells, Cultured, In Situ Hybridization
Lymphokines, Cell Death, Gene Expression Regulation, Developmental, Endothelial Growth Factors, AMP-Activated Protein Kinases, Embryo, Mammalian, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, DNA-Binding Proteins, Mesoderm, Mice, Inbred C57BL, Embryonic and Fetal Development, Mice, Gene Targeting, Animals, Blood Vessels, Endothelium, Vascular, Hypoxia-Inducible Factor 1, Cells, Cultured, In Situ Hybridization
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