| Abstrakt: |
Vascular endothelial growth factor receptor 3 (VEGFR‐3) is required for cardiovascular development during embryogenesis. In adults, this receptor is expressed in lymphatic endothelial cells, and mutant VEGFR3alleles have been implicated in human hereditary lymphedema. To better understand the basis of its specific endothelial lineage‐restricted expression, we have characterized the VEGFR3gene and its regulatory 5′ flanking region. The human gene contains 31 exons, of which exons 30a and 30b are alternatively spliced. The VEGFR3proximal promoter is TATA‐less and contains stretches of sequences homologous with the mouse Vegfr3promoter region. In transfection experiments of cultured cells, the Vegfr3promoter was shown to control endothelial cell‐specific transcription of downstream reporter genes. This result was further confirmed in vivo;in a subset of transgenic mouse embryos, a 1.6 kb Vegfr3promoter fragment directed weak lymphatic endothelial expression of the LacZmarker gene. This suggests that endothelial cell‐specific elements occur in the proximal promoter, although further enhancer elements are probably located elsewhere. The sequence, organization, and variation in the VEGFR3gene and its regulatory region provide important tools for the molecular genetic analysis of the lymphatic system and its disorders.—Iljin, K., Karkkainen, M. J., Lawrence, E. C., Kimak, M. A., Uutela, M., Taipale, J., Pajusola, K., Alhonen, L., Halmekyto, M., Finegold, D. N., Ferrell, R. E., Alitalo, K. VEGFR3gene structure, regulatory region, and sequence polymorphisms. FASEB J.15, 1028–1036 (2001) |
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