Differential expression of VEGF isoforms in mouse during development and in the adult.

Published

Journal Article

Vascular endothelial growth factor (VEGF), a factor that is critical for development of the vascular system in mouse embryos, exists as at least three isoforms, VEGF120, VEGF164, and VEGF188. The isoforms have different affinities for heparan sulfate as well as for the three known VEGF receptors, VEGFR-1 (Flt-1), VEGFR-2 (Flk-1), and neuropilin-1, suggesting that different VEGF isoforms may play distinct roles in vascular development. To determine whether there are differences in the organ-specific expression patterns that would support this concept, we used a quantitative RNase protection assay (RPA) to determine the distribution of different VEGF isoform mRNA in developing and adult mouse organs. Results revealed that the ratios of the three VEGF isoforms changed during organ development and that adult organs expressed different levels of the three VEGF isoforms. Because the lung expressed the highest levels of VEGF188 isoform, we used VEGF isoform-specific in situ hybridization in the developing lung and determined that type II alveolar epithelial cells were expressing high levels of VEGF188 mRNA. Finally, targeted exon deletion of the VEGF gene revealed that mice that developed in the absence of the heparan sulfate binding isoforms VEGF164 and VEGF188, displayed a variety of vascular defects, including abnormal pulmonary vascular development. Our results support the concept that different VEGF isoforms have distinct functions in vascular development.

Full Text

Duke Authors

Cited Authors

  • Ng, YS; Rohan, R; Sunday, ME; Demello, DE; D'Amore, PA

Published Date

  • February 2001

Published In

Volume / Issue

  • 220 / 2

Start / End Page

  • 112 - 121

PubMed ID

  • 11169844

Pubmed Central ID

  • 11169844

Electronic International Standard Serial Number (EISSN)

  • 1097-0177

International Standard Serial Number (ISSN)

  • 1058-8388

Digital Object Identifier (DOI)

  • 10.1002/1097-0177(2000)9999:9999<::aid-dvdy1093>3.0.co;2-d

Language

  • eng