Abstract
We describe the genomic organization and functional characterization of the mouse gene encoding vascular endothelial growth factor (VEGF), a polypeptide implicated in embryonic vascular development and postnatal angiogenesis. The coding region for mouse VEGF is interrupted by seven introns and encompasses approximately 14 kilobases. Organization of exons suggests that, similar to the human VEGF gene, alternative splicing generates the 120-, 164-, and 188-amino acid isoforms, but does not predict a fourth VEGF isoform corresponding to human VEGF206. Approximately 1. 2 kilobases of 5'-flanking region have been sequenced, and primer extension analysis identified a single major transcription initiation site, notably lacking TATA or CCAT consensus sequences. The 5'-flanking region is sufficient to promote a 7-fold induction of basal transcription. The genomic region encoding the 3'-untranslated region was determined by Northern and nuclease mapping analysis. Investigation of mRNA sequences responsible for the rapid turnover of VEGF mRNA (mRNA half-life, <1 h) (Shima, D. T. , Deutsch, U., and D'Amore, P. A. (1995) FEBS Lett. 370, 203-208) revealed that the 3'-untranslated region was sufficient to trigger the rapid turnover of a normally long-lived reporter mRNA in vitro. These data and reagents will allow the molecular and genetic analysis of mechanisms that control the developmental and pathological expression of VEGF.
Highlights
We describe the genomic organization and functional characterization of the mouse gene encoding vascular endothelial growth factor (VEGF), a polypeptide implicated in embryonic vascular development and postnatal angiogenesis
One of these clones, designated lambda 8, overlapped with regions represented in a VEGF cosmid clone; these two clones were used for structural analysis of the VEGF gene
The presence of significant VEGF mRNA and protein in various tissues of the adult suggests an additional role for VEGF in the maintenance of normal vascular cell integrity and/or behavior [4]
Summary
We describe the genomic organization and functional characterization of the mouse gene encoding vascular endothelial growth factor (VEGF), a polypeptide implicated in embryonic vascular development and postnatal angiogenesis. 370, 203–208) revealed that the 3-untranslated region was sufficient to trigger the rapid turnover of a normally long-lived reporter mRNA in vitro These data and reagents will allow the molecular and genetic analysis of mechanisms that control the developmental and pathological expression of VEGF. The spatial and temporal expression patterns of VEGF and its tyrosine kinase receptors, flt-1 and flk-1/KDR, during periods of blood vessel growth have led investigators to suggest a paracrine role for VEGF during the development of the embryonic vasculature [11, 12]. In which the flk-1 receptor was deleted by targeted disruption, lacked blood islands and died between days 8.5 and 9.5 In these embryos, no organized blood vessels were observed and hematopoiesis was dramatically reduced [14]. In which flt-1 was mutated by targeted disruption, were able to form endothelial cells but unable to assemble them into normal vascular channels and died at mid-somite stages [15]
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