Knockout Mouse Catalog | Cyagen APAC


>> Request a Quote or Information
Our Experts will contact you providing a quote,
information and estimated timeframe to
your project needs.

Product Number:C001395

Genetic Background:C57BL/6J

Reproduction:Carriers x WT

Strain Description

The Vascular Endothelial Growth Factor (VEGF) family is a group of highly specific 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 TG-VEGFA mouse is a transgenic model generated by Cyagen in C57BL/6J mice. In this model, the expression of human VEGFA CDS is driven by the bovine rhodopsin promoter, allowing for specific overexpression of the human VEGFA gene in the retina without affecting the expression of the endogenous VEGFA gene. This model exhibits clear retinal and choroidal vascular lesions while maintaining complete eye structure and can naturally develop diseases. Anti-VEGF drugs such as Aflibercept[4] have been evaluated for efficacy in this mouse model, demonstrating that Aflibercept can target and suppress VEGF expression, thereby alleviating retinal vascular lesions. As such, this model is well-suited for drug evaluation and mechanism research related to neovascular ophthalmic diseases.


Figure 1. Diagram of the gene editing strategy employed in the generation of TG-VEGFA mice. Utilizing transgenic technology, the “Bovine rhodopsin promoter-Kozak-Human VEGFA CDS-Mouse Prm1 polyA” gene expression construct was successfully integrated into the mouse genome. This approach facilitated the specific overexpression of human VEGFA in the retina of TG-VEGFA mice.

● Research on Age-Related Macular Degeneration (AMD);

● Research on Diabetic Retinopathy (DR);

● Research on corneal neovascular diseases.

1.Expression of human VEGFA and mouse VEGFA gene

Figure 2. Detection of human VEGFA and mouse VEGFA expression in TG-VEGFA mice and wild-type mice. The qPCR analysis revealed that both human and murine VEGFA genes were expressed in TG-VEGFA mice. The expression level of murine VEGFA was comparable to that in wild-type mice, indicating that the presence of human VEGFA did not affect murine VEGFA expression.


2.Retinal morphology and retinal vasculature

Figure 3. Fundus and retina morphology of 6-week-old TG-VEGFA mice and C57BL/6J wild-type mice. The results of retinal optical coherence tomography (OCT) assays showed a slight structural disorder in the choroidal region of TG-VEGFA mice compared to the wild type.


3.Fundus Fluorescence Angiography (FFA) of F0-generation TG-VEGFA mice

Figure 4. Results of Fundus Fluorescein Angiography (FFA) in 6-week-old F0-generation TG-VEGFA mice and C57BL/6J wild-type mice. The ocular vessels of the mice were observed by FFA angiography, and the results showed that the fundus of TG-VEGFA mice (F0) showed vascular lesions as large fluorescein sodium leakage compared to the wild type.


4.Fundus Fluorescence Angiography (FFA) of F1- and F2-generation TG-VEGFA mice

Figure 5. The FFA in F1- and F2-generation TG-VEGFA mice. F1- and F2-generation TG-VEGFA mice exhibited a vasculopathy phenotype with large sodium fluorescein leaks, similar to the F0-generation TG-VEGFA mice.


5.Electroretinogram (ERG) Examination

Figure 6. Electroretinogram (ERG) results of TG-VEGFA and wild-type mice (C57BL/6J). Retinal potentials of TG-VEGFA mice (hVEGF) were not significantly different from those of wild-type mice (WT) for the time being.


6.H&E staining of the retina

Figure 7. H&E staining results in the eyes of TG-VEGFA and wild-type mice. The results of H&E staining revealed a pathological phenotype of vascular proliferation in the retinal area of TG-VEGFA mice compared to wild-type (C57BL/6J) mice.


7.Retinal and choroidal isolectin GS-lB4 immunostaining

Figure 8. Results of retinal and choroidal Isolectin GS-lB4 staining in TG-VEGFA and wild-type mice. IB4 staining of the retina and choroid revealed abnormal blood vessel proliferation and structural disorder in the retina of TG-VEGFA mice compared to wild-type mice (C57BL/6J), abnormal proliferation was also observed in the choroid area.


8.Pharmacodynamic evaluation of Aflibercept

Figure 9. Pharmacodynamic validation of VEGF-targeted drug, Aflibercept, in TG-VEGFA mice. Before Aflibercept injection, TG-VEGFA mice exhibited obvious vascular lesions and large areas of fluorescein sodium leakage in the fundus. After Aflibercept injection, vascular lesions were significantly reduced and the area of eye lesions decreased. And with continued injections, ocular lesions gradually decreased until disappeared.

Route of administration: 3 μg/eye/week, intravitreal injection.

High-level expression of human VEGFA in TG-VEGFA mice does not affect endogenous mouse VEGFA expression. This model exhibits retinal structural disorder, vascular proliferation, and large-area vascular leakage. Structural disorder and vascular proliferation are also present in the choroid. Aflibercept, an anti-VEGFA drug, can reduce vascular leakage and alleviates ocular vascular lesions in TG-VEGFA mice.

In summary, TG-VEGFA mice overexpress human VEGFA and naturally develop ocular retinal and choroidal lesions while maintaining intact eyeball structures. Anti-VEGFA drugs effectively alleviate ocular lesions. This model is suitable for drug evaluation and mechanism research of neovascular-related ophthalmic diseases.



[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] Stewart MW, Grippon S, Kirkpatrick P. Aflibercept. Nat Rev Drug Discov. 2012 Mar 30;11(4):269-70.Hartong, D. T., Berson, E. L., & Dryja, T. P. (2006). Retinitis pigmentosa. The Lancet, 368(9549), 1795-1809.