B6-hVEGFA Mice

Catalog Number: C001555

Strain Name: C57BL/6JCya-Vegfatm1(hVEGFA)/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote

One of Cyagen’s HUGO-GTTM (Humanized Genomic Ortholog for Gene Therapy) Strains

 

Strain Description

The Vascular Endothelial Growth Factor (VEGF) family is a group of particular endothelial growth factors intimately associated with angiogenesis. These factors promote increased vascular permeability, extracellular matrix degeneration, vascular endothelial cell migration and proliferation, and are capable of stimulating angiogenesis and increasing the permeability of existing vessels. As such, they play a pivotal role in normal vascular development and wound healing. The VEGF family comprises VEGFA, VEGFB, VEGFC, VEGFD, VEGFE, and PLGF [1]. Of these, VEGFA is the most commonly targeted in research related to neovascular ophthalmic diseases due to its crucial role in the proliferation, migration, and formation of endothelial cell microvessels [2]. Overexpression of VEGFA in the eye can result in abnormal vascular growth and leakage, leading to various ophthalmic diseases such as Age-Related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and corneal neovascularization [2-3]. The progression of solid tumors depends on vascularization and angiogenesis within malignant tissues, with VEGFA playing a crucial role among various pro-angiogenic factors. The VEGFA gene is upregulated in many known tumors, correlating with tumor staging and progression. Blocking VEGFA may lead to vascular network regression, thereby inhibiting tumor growth. Thus, VEGFA is an important target for anti-angiogenic cancer therapies.

The B6-hVEGFA mice were generated by replacing the mouse Vegfa gene sequence with the human VEGFA gene sequence, including the non-coding 3’ UTR region. This model expresses the human VEGFA protein. B6-hVEGFA mice can be used for mechanistic studies and efficacy evaluations of ophthalmic diseases such as Age-Related Macular Degeneration (AMD), Diabetic Retinopathy (DR), and corneal neovascularization, as well as for tumor development and cancer drug research.

Strain Strategy


Figure 1. Gene editing strategy of B6-hVEGFA mice. The sequence from the CTG start codon to 3'UTR of the mouse Vegfa gene was replaced with the sequence from the CTG start codon to 3'UTR of the human VEGFA gene.

Application

  • Research on Age-Related Macular Degeneration (AMD);
  • Research on Diabetic Retinopathy (DR);
  • Research on corneal neovascular diseases;
  • Tumor development and cancer drug research.

Validation Data

1. Normal retinal morphology and vasculature in B6-hVEGFA mice


Figure 2. Fundus morphology, OCT, and FFA results of wild-type and B6J-hVEGFA mice. The fundus morphology, retinal OCT, and fundus fluorescein angiography results of heterozygous and homozygous B6J-hVEGFA mice were consistent with those of WT.

2. Normal photoreceptor function in B6-hVEGFA mice


Figure 3. Electroretinogram (ERG) detection results of WT and B6J-hVEGFA mice. Compared with WT, the amplitudes of the a-wave and b-wave in both scotopic and photopic ERG recordings of heterozygous and homozygous B6J-hVEGFA mice were nearly identical to those of the WT. The retinal photoreceptor function of heterozygous and homozygous B6J-hVEGFA mice were normal.

 

 

References

[1] Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004 Dec;56(4):549-80.
[2] Apte RS, Chen DS, Ferrara N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell. 2019 Mar 7;176(6):1248-1264.
[3] Mesquita J, Castro-de-Sousa JP, Vaz-Pereira S, Neves A, Passarinha LA, Tomaz CT. Vascular endothelial growth factors and placenta growth factor in retinal vasculopathies: Current research and future perspectives. Cytokine Growth Factor Rev. 2018 Feb;39:102-115.
[4] Chekhonin VP, Shein SA, Korchagina AA, Gurina OI. VEGF in tumor progression and targeted therapy. Curr Cancer Drug Targets. 2013 May;13(4):423-43.