Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice

A. Ylikorkala, D. J. Rossi, N. Korsisaari, K. Luukko, K. Alitalo, M. Henkemeyer, T. P. Mäkelä

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Abstract

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 Lkb 1 in the VEGF signaling pathway and suggest that the vascular defects accompanying Lkb 1 loss are mediated at least in part by VEGF.

Original languageEnglish (US)
Pages (from-to)1323-1326
Number of pages4
JournalScience
Volume293
Issue number5533
DOIs
Publication statusPublished - Aug 17 2001

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Ylikorkala, A., Rossi, D. J., Korsisaari, N., Luukko, K., Alitalo, K., Henkemeyer, M., & Mäkelä, T. P. (2001). Vascular abnormalities and deregulation of VEGF in Lkb1-deficient mice. Science, 293(5533), 1323-1326. https://doi.org/10.1126/science.1062074