B6-hRHO-P23H Mouse
Product Name
B6-hRHO-P23H Mouse
Product ID
C001495
Strain Name
C57BL/6JCya-Rhotm2(hRHO*P23H)/Cya
Backgroud
C57BL/6JCya
When using this mouse strain in a publication, please cite “B6-hRHO-P23H Mouse (Catalog C001495) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
RP4, OPN2, CSNBAD1
NCBI ID
Chromosome
Chr 3
MGI ID
Datasheet
Strain Description
Retinitis pigmentosa (RP) is a hereditary retinal disease with a global prevalence of approximately 1:5000-1:3000. RP is highly clinically and genetically heterogeneous, with mutations in the rhodopsin (RHO) gene causing approximately 25% of dominant RP [1]. The rhodopsin encoded by the RHO gene is closely associated with visual light transduction and GPCR downstream signals. Rhodopsin is essential for the transmission of light signals in the process of vision formation. Most RHO mutations lead to high levels of rhodopsin expression in photoreceptor cells, causing many mutant proteins to be abnormally located and aggregated in cells. This results in the apoptosis of photoreceptor cells, which cannot perform normal light signal transduction functions. Additionally, mutations in the RHO gene are associated with congenital stationary night blindness (CSNB) [2-6]. Current gene therapy targeting the RHO gene to treat retinitis pigmentosa includes ASO, CRISPR, and others. Applying fully humanized animal models will promote the further development of RHO-related potential therapies in clinical trials [7-12].
This strain is a mouse Rho gene humanized model, in which the endogenous mouse Rho gene is replaced by the human RHO gene carrying a P23H mutation to express human retinal proteins in mice. Therefore, the abnormal protein encoded by the human gene was expressed in mice, resulting in abnormal retinal appearance and function and visual defects in this model. Based on the self-developed technological innovation of TurboKnockout fusion BAC recombination, Cyagen can also provide customized services for different point mutations to meet the needs of a wide range of R&D personnel regarding the pharmacodynamics of retinitis pigmentosa (RP) and other preclinical needs.
Mutations in the RHO gene can lead to rhodopsin-mediated autosomal dominant retinitis pigmentosa (RHO-adRP). In 25% of autosomal dominant inherited RP (adRP) cases, there are over 150 different RHO gene mutations. Notably, the P23H mutation is one of the most prevalent, accounting for 10% of adRP cases [2]. Previous studies have shown that mice carrying the heterozygous human RHO P23H mutation exhibit retinopathy and progressive retinal degeneration similar to the patient's disease process, which could be used for visual signaling and retinitis pigmentosa (RP) studies [3]. B6-hRHO-P23H homozygous mice develop the disease earlier and have a more severe phenotype than heterozygous mice. Considering the uncertainty of growth and survival of homozygous mice due to late blindness, it is recommended to use B6-hRHO-P23H heterozygous mice for experiments. However, homozygous mice may also be selected for research according to specific experimental needs.
Reference
Hartong, D. T., Berson, E. L., & Dryja, T. P. (2006). Retinitis pigmentosa. The Lancet, 368(9549), 1795-1809.
Meng D, Ragi SD, Tsang SH. Therapy in Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa. Mol Ther. 2020 Oct 7;28(10):2139-2149.
Sakami S, Maeda T, Bereta G, Okano K, Golczak M, Sumaroka A, Roman AJ, Cideciyan AV, Jacobson SG, Palczewski K. Probing mechanisms of photoreceptor degeneration in a new mouse model of the common form of autosomal dominant retinitis pigmentosa due to P23H opsin mutations. J Biol Chem. 2011 Mar 25;286(12):10551-67.
Dryja, T. P., McGee, T. L., Reichel, E., Hahn, L. B., Cowley, G. S., Yandell, D. W., ... & Berson, E. L. (1990). A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature, 343(6256), 364-366.
Zhang, X., Fu, W., Pang, C. P., & Yeung, K. Y. (2002). Screening for point mutations in rhodopsin gene among one hundred Chinese patients with retinitis pigmentosa. Zhonghua yi xue yi Chuan xue za zhi= Zhonghua Yixue Yichuanxue Zazhi= Chinese Journal of Medical Genetics, 19(6), 463-466.
Gamundi, M. J., Hernan, I., Muntanyola, M., Maseras, M., López‐Romero, P., Alvarez, R., ... & Carballo, M. (2008). Transcriptional expression of cis‐acting and trans‐acting splicing mutations cause autosomal dominant retinitis pigmentosa. Human mutation, 29(6), 869-878.
Biasutto, P., Adamson, P. S., Dulla, K., Murray, S., Monia, B., & McCaleb, M. (2019). Allele specific knock-down of human P23H rhodopsin mRNA and prevention of retinal degeneration in humanized P23H rhodopsin knock-in mouse, following treatment with an intravitreal GAPmer antisense oligonucleotide (QR-1123). Investigative Ophthalmology & Visual Science, 60(9), 5719-5719.
Editas Medicine, Inc. (2022, October 13). Press Release: Editas Medicine Presents Preclinical Data On EDIT-103 For Rhodopsin-Associated Autosomal Dominant Retinitis Pigmentosa At The European Society Of Gene And Cell Therapy Annual Meeting. Editasmedicine. https://ir.editasmedicine.com/news-releases/news-release-details/editas-medicine-presents-preclinical-data-edit-103-rhodopsin-0.
Patrizi, C., Llado, M., Benati, D., Iodice, C., Marrocco, E., Guarascio, R., ... & Recchia, A. (2021). Allele-specific editing ameliorates dominant retinitis pigmentosa in a transgenic mouse model. The American Journal of Human Genetics, 108(2), 295-308.
Li, P., Kleinstiver, B. P., Leon, M. Y., Prew, M. S., Navarro-Gomez, D., Greenwald, S. H., ... & Liu, Q. (2018). Allele-specific CRISPR-Cas9 genome editing of the single-base P23H mutation for rhodopsin-associated dominant retinitis pigmentosa. The CRISPR journal, 1(1), 55-64.
Liu, X., Jia, R., Meng, X., Li, Y., & Yang, L. (2022). Retinal degeneration in humanized mice expressing mutant rhodopsin under the control of the endogenous murine promoter. Experimental Eye Research, 215, 108893.
Wu, W. H., Tsai, Y. T., Huang, I. W., Cheng, C. H., Hsu, C. W., Cui, X., ... & Tsang, S. H. (2022). CRISPR genome surgery in a novel humanized model for autosomal dominant retinitis pigmentosa. Molecular Therapy, 30(4), 1407-1420.
ProQR Therapeutics. (2024). ProQR Receives Fast Track Designation from FDA for QR-1123 for Autosomal Dominant Retinitis Pigmentosa. Retrieved from ProQR Receives Fast Track Designation from FDA for QR-1123 for Autosomal Dominant https://www.proqr.com/press-releases/proqr-receives-fast-track-designation-from-fda-for-qr-1123-for-autosomal-dominant
Strain Strategy
Figure 1. Diagram of the gene editing strategy for the generation of B6-hRHO-P23H mice. The sequences from the ATG start codon to the downstream part of the 3'UTR of the endogenous mouse Rho gene were replaced with the sequences from the ATG start codon to the downstream part of the 3'UTR of the human RHO gene and the point mutation p.P23H (CCC to CAC) was introduced into exon1 of human RHO gene.
Application Area
Research on retinitis pigmentosa (RP);
Research on congenital stationary night blindness (CSNB);
Research on other retinal diseases.
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