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Contrasting properties of VEGF165 and VEGF165b splicing isoforms on glomerular water permeability in transgenic mice and complementary rescue of the phenotype
Author(s) -
Oltean Sebastian,
Ferguson Joanne,
Qiu Yan,
Salmon Andrew H,
Quaggin Susan,
Harper Steve J,
Bates David O
Publication year - 2010
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/fasebj.24.1_supplement.774.12
Subject(s) - genetically modified mouse , transgene , in vivo , alternative splicing , gene isoform , permeability (electromagnetism) , vascular permeability , chemistry , in vitro , microbiology and biotechnology , biology , medicine , endocrinology , gene , biochemistry , genetics , membrane
VEGF is a major regulator of vascular permeability and increases glomerular permeability to water (LPA/Vi) in vitro on isolated intact glomeruli (1). In a double‐transgenic mouse model of kidney‐specific inducible VEGF expression a time‐dependent increase in LPA/Vi in double‐transgenic animals treated with Doxycycline compared with wild‐type mice was observed. VEGF165b, a splicing variant resulting from the use of a tandem 3' splice site in exon 8 of the VEGF gene, differs in six amino acids at the C‐terminal end of VEGF. VEGF165b decreases glomerular permeability to water both in vitro as well as in vivo in a transgenic mouse model of VEGF165b over‐expression in kidneys. To determine whether the decreased glomerular permeability phenotype in mice over‐expressing VEGF165b can be rescued by VEGF, paired permeability measurements were performed on glomeruli isolated from heterozygote mice before and after incubation in 1nM rhVEGF for 60 minutes. There was a significant increase in LPA/Vi from 1.67±0.32 to 2.57±0.58, indicating that the decreased permeability in VEGF165b expressing mice is reversible.