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VEGFR3 gene structure, regulatory region, and sequence polymorphisms
Author(s) -
Iljin Kristiina,
Karkkainen Marika J.,
Lawrence Elizabeth C.,
Kimak Mark A.,
Uutela Marko,
Taipale Jussi,
Pajusola Katri,
Alhonen Leena,
HalmekytÖ Maria,
Finegold David N.,
Ferrell Robert E.,
Alitalo Kari
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fsb2fj000383com
Subject(s) - biology , enhancer , gene , exon , microbiology and biotechnology , promoter , regulatory sequence , genetics , regulation of gene expression , gene expression
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 VEGFR3 alleles have been implicated in human hereditary lymphedema. To better understand the basis of its specific endothelial lineage‐restricted expression, we have characterized the VEGFR3 gene and its regulatory 5′ flanking region. The human gene contains 31 exons, of which exons 30a and 30b are alternatively spliced. The VEGFR3 proximal promoter is TATA‐less and contains stretches of sequences homologous with the mouse Vegfr3 promoter region. In transfection experiments of cultured cells, the Vegfr3 promoter 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 Vegfr3 promoter fragment directed weak lymphatic endothelial expression of the LacZ marker 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 VEGFR3 gene 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. VEGFR3 gene structure, regulatory region, and sequence polymorphisms. FASEB J. 15, 1028–1036 (2001)