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The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess the effects of splicing regulatory compounds in vivo

Stevens, M. ; Star, E. ; Lee, M. ; Innes, E. ; Li, L. ; Bowler, E. ; Harper, S. ; Bates, D. O. ; Oltean, S.

RNA biology, 2019-12, Vol.16 (12), p.1672-1681 [Periódico revisado por pares]

United States: Taylor & Francis

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Título:
The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess the effects of splicing regulatory compounds in vivo
Autor: Stevens, M. ; Star, E. ; Lee, M. ; Innes, E. ; Li, L. ; Bowler, E. ; Harper, S. ; Bates, D. O. ; Oltean, S.
Assuntos: Alternative Splicing ; angiogenesis ; Animals ; Animals, Genetically Modified ; Exons ; Eye - metabolism ; Genes, Reporter ; Genetic Loci ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Introns ; Kidney - metabolism ; Luminescent Proteins - genetics ; Luminescent Proteins - metabolism ; Mice ; mouse model ; Muscle, Skeletal - metabolism ; Myocardium - metabolism ; Pancreas - metabolism ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Kinase Inhibitors - pharmacology ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Protein-Serine-Threonine Kinases - genetics ; Protein-Serine-Threonine Kinases - metabolism ; Research Paper ; splicing-sensitive fluorescent reporter ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; vascular endothelial growth factor-A
É parte de: RNA biology, 2019-12, Vol.16 (12), p.1672-1681
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Vascular endothelial growth factor (VEGF)-A is differentially spliced to give two functionally different isoform families; pro-angiogenic, pro-permeability VEGF-A xxx and anti-angiogenic, anti-permeability VEGF-A xxx b. VEGF-A splicing is dysregulated in several pathologies, including cancer, diabetes, and peripheral arterial disease. The bichromatic VEGF-A splicing-sensitive fluorescent reporter harboured in a transgenic mouse is a novel approach to investigate the splicing patterns of VEGF-A in vivo. We generated a transgenic mouse harbouring a splicing-sensitive fluorescent reporter designed to mimic VEGF-A terminal exon splicing (VEGF8ab) by insertion into the ROSA26 genomic locus. dsRED expression denotes proximal splice site selection (VEGF-A xxx ) and eGFP expression denotes distal splice site selection (VEGF-A xxx b). We investigated the tissue-specific expression patterns in the eye, skeletal muscle, cardiac muscle, kidney, and pancreas, and determined whether the splicing pattern could be manipulated in the same manner as endogenous VEGF-A by treatment with the SRPK1 inhibitor SPHINX 31. We confirmed expression of both dsRED and eGFP in the eye, skeletal muscle, cardiac muscle, kidney, and pancreas, with the highest expression of both fluorescent proteins observed in the exocrine pancreas. The ratio of dsRED and eGFP matched that of endogenous VEGF-A xxx and VEGF-A xxx b. Treatment of the VEGF8ab mice with SPHINX 31 increased the mRNA and protein eGFP/dsRED ratio in the exocrine pancreas, mimicking endogenous VEGF-A splicing. The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess splicing regulation in the individual cell-types and tissues, which provides a useful screening process for potentially therapeutic splicing regulatory compounds in vivo
Editor: United States: Taylor & Francis
Idioma: Inglês

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The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess the effects of splicing regulatory compounds in vivo

Stevens, M. ; Star, E. ; Lee, M. ; Innes, E. ; Li, L. ; Bowler, E. ; Harper, S. ; Bates, D. O. ; Oltean, S.

United States: Taylor & Francis

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