Product Number：C001425
Genetic Background：C57BL/6J
Reproduction：Homozygote x Homozygote
Strain Description
The NR2E3 gene encodes an orphan nuclear receptor in retinal photoreceptor cells, which is a ligand-dependent transcription factor. The NR2E3 protein is part of a large family of nuclear receptor transcription factors that regulate signaling pathways involved in embryonic development and the maintenance of normal cellular function in adults. As a transcription factor, NR2E3 acts as an activator of rod cell development and an inhibitor of cone cell development, binding to the promoter regions of several rod- and cone-specific genes, including rhodopsin (RHO), M- and S-cone opsins (OPN1MW/OPN1SW), and the rod-specific phosphodiesterase beta subunit (PDE6B). [1] NR2E3 enhances the expression of rhodopsin and inhibits the expression of M- and S-cone opsins. Mutations in the NR2E3 gene are associated with Enhanced S-Cone Syndrome (ESCS) and retinitis pigmentosa (RP). Under normal conditions, the retina contains “red,” “blue,” and “green” cone cells, allowing people to see colors correctly. In ESCS, there are more blue cone cells than normal, and the rod cells, as well as the red and green cone cell receptors, degenerate. Patients often present with night blindness during childhood, with other symptoms including accommodative esotropia, nystagmus, decreased visual acuity, day blindness, and retinal lesions. Most patients have coin-shaped pigment changes along the vascular arcades and yellow-white subretinal lesions in the posterior pole, which later progress to more typical pigmentary lesions. [2]
This strain is a mouse Nr2e3 knockout model that uses gene editing technology to knock out the homolog of the human NR2E3 gene in mice. The absence of the Nr2e3 gene in mice can lead to the appearance of pathological retinal spots, late-onset retinal degeneration, reduced ERG amplitude in rod cells, and folding and vortices in the photoreceptor layer.[3-4] The Nr2e3 KO mice can be used as a model for enhanced S-cone syndrome (ESCS) research.
The mouse Nr2e3 gene is located on chromosome 9, and exon 4-5 of this gene was knocked out using gene editing techniques.
● Enhanced S-Cone Syndrome (ESCS) Research;
● Retinitis Pigmentosa (RP) Research;
● Other Retinal Diseases Research.
1. Optical coherence tomography (OCT) of the retina
Figure 1. Optical coherence tomography (OCT) of 4-week-old wild-type mice (WT), heterozygous Nr2e3 KO mice (HE), and homozygous Nr2e3 KO mice (HO). Compared to wild-type mice, homozygous Nr2e3 KO mice have obvious yellow-white subretinal spot lesions in the eyes.
2. Electroretinogram (ERG) testing
Figure 2. Electroretinogram (ERG) of homozygous Nr2e3 KO mice and wild-type mice (C57BL/6J). The amplitudes of a-waves in the scotopic ERG of Nr2e3 KO mice were lower than wild-type mice, indicating an impairment in light perception in the eyes of Nr2e3 KO mice.
Retinal pathology evaluation of Nr2e3 KO mice and wild-type (WT) mice was performed using Electroretinogram (ERG) and optical coherence tomography (OCT). The results showed that, compared to wild-type mice, the retina of Nr2e3 KO mice had obvious yellow-white pathological spots and a reduced amplitude of the a-wave in scotopic ERG, indicating the presence of retinitis pigmentosa and photoreceptor dysfunction in this model. This model can be used for the study of retinal diseases such as Enhanced S-Cone Syndrome (ESCS) and retinitis pigmentosa (RP).
References
[1] Schorderet DF, Escher P. NR2E3 mutations in enhanced S-cone sensitivity syndrome (ESCS), Goldmann-Favre syndrome (GFS), clumped pigmentary retinal degeneration (CPRD), and retinitis pigmentosa (RP). Hum Mutat. 2009 Nov;30(11):1475-85.
[2] Tsang SH, Sharma T. Enhanced S-Cone Syndrome (Goldmann-Favre Syndrome). Adv Exp Med Biol. 2018;1085:153-156.
[3] Venturini G, Kokona D, Steiner BL, Bulla EG, Jovanovic J, Zinkernagel MS, Escher P. In vivo analysis of onset and progression of retinal degeneration in the Nr2e3rd7/rd7 mouse model of enhanced S-cone sensitivity syndrome. Sci Rep. 2021 Sep 24;11(1):19032.
[4] Chakraborty D, Conley SM, Naash MI. Overexpression of retinal degeneration slow (RDS) protein adversely affects rods in the rd7 model of enhanced S-cone syndrome. PLoS One. 2013 May 1;8(5):e63321.