Rho KO Mice

Catalog Number: C001700

Strain Name: C57BL/6JCya-Rhoem4/Cya

Genetic Background: C57BL/6JCya

Reproduction: Homozygote x Homozygote

 

Strain Description

The Rhodopsin gene ( RHO ) is predominantly expressed in rod photoreceptor cells of the retina, where it encodes rhodopsin, a G protein-coupled receptor crucial for scotopic vision. Functioning as a light-sensitive pigment, rhodopsin initiates phototransduction upon photon absorption, triggering neural signaling to the brain [1]. Restricted to rod cells within the neural retina, mutations in RHO are a major etiological factor in inherited retinal degenerations, notably autosomal dominant retinitis pigmentosa (RP), characterized by progressive rod photoreceptor dysfunction leading to night blindness and tunnel vision [2-3]. Furthermore, RHO mutations are implicated in congenital stationary night blindness (CSNB) and Leber congenital amaurosis (LCA) [4]. Studies have shown that homozygous Rho knockout (KO) mice, due to the absence of functional rhodopsin protein, exhibit failure of rod outer segment formation or rapid degeneration, leading to severe retinal degeneration and vision loss early after birth. Heterozygous Rho KO mice, on the other hand, display a slower, progressive retinal degeneration and functional decline [5-6]. Therefore, Rho KO mice can model human retinal diseases caused by complete loss of RHO function, such as certain autosomal recessive retinitis pigmentosa (arRP) or Leber congenital amaurosis (LCA), but are not suitable for modeling the most common autosomal dominant retinitis pigmentosa (adRP) caused by RHO mutations (e.g., the toxic protein produced by the P23H mutation) [7].

The Rho KO mouse is a gene knockout model created using gene-editing techniques to knock out the coding sequence of the Rho gene (the homolog of the human RHO gene) in mice. The validation data shows that this model exhibits significant thinning of the outer nuclear layer (ONL) of the retina and abnormalities in electroretinography (ERG), effectively mimicking human disease phenotypes. Therefore, it can be used to study the pathogenic mechanisms of retinitis pigmentosa and congenital stationary night blindness, as well as for the research and development of related therapeutic interventions.

 

Strain Strategy

The mouse Rho gene in mice consists of 5 exons, with the start codon in exon 1 and the stop codon in exon 5. This strain was created by gene-editing techniques that knocked out the region spanning exons 2 ~ 4.


Application

  • Research on retinitis pigmentosa (RP);
  • Research on congenital stationary night blindness (CSNB);
  • Research on other retinal diseases.

 

Validation Data

1. Retinal phenotypes in WT, and Rho KO mice


Figure 1. Fundus morphology, Optical Coherence Tomography (OCT), and Fluorescein Fundus Angiography (FFA) results of wild type (WT), and 8-week-old homozygous Rho KO mice. Compared with the wild-type, the outer nuclear layer (ONL) of the retina was significantly thinner in homozygous RHO-KO mice than in wild-type mice.

*OD: Oculus Dexter; OS: Oculus Sinister

 

2. Electroretinogram (ERG) in WT, and Rho KO mice


Figure 2. Electroretinogram (ERG) detection results of WT and RHO-KO mice Compared with WT, the amplitudes of the scotopic a-wave, b-wave and photopic a-wave of the B6-RHO-KO mice were significantly reduced, and the amplitudes of the photopic b-wave were normal.

 

References
[1]Hofmann KP, Lamb TD. Rhodopsin, light-sensor of vision. Prog Retin Eye Res. 2023 Mar;93:101116.
[2]Meng D, Ragi SD, Tsang SH. Therapy in Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa. Mol Ther. 2020 Oct 7;28(10):2139-2149.
[3]Hofmann L, Palczewski K. The G protein-coupled receptor rhodopsin: a historical perspective. Methods Mol Biol. 2015;1271:3-18.
[4]Athanasiou D, Aguila M, Bellingham J, Li W, McCulley C, Reeves PJ, Cheetham ME. The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy. Prog Retin Eye Res. 2018 Jan;62:1-23.
[5]Humphries MM, Rancourt D, Farrar GJ, Kenna P, Hazel M, Bush RA, Sieving PA, Sheils DM, McNally N, Creighton P, Erven A, Boros A, Gulya K, Capecchi MR, Humphries P. Retinopathy induced in mice by targeted disruption of the rhodopsin gene. Nat Genet. 1997 Feb;15(2):216-9.
[6]Lem J, Krasnoperova NV, Calvert PD, Kosaras B, Cameron DA, Nicolò M, Makino CL, Sidman RL. Morphological, physiological, and biochemical changes in rhodopsin knockout mice. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):736-41.
[7]Athanasiou D, Aguila M, Bellingham J, Li W, McCulley C, Reeves PJ, Cheetham ME. The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy. Prog Retin Eye Res. 2018 Jan;62:1-23.