智鼠故事 
B6-hRHO (Promoter)小鼠
复苏/繁育服务
产品名称
B6-hRHO (Promoter)
产品编号
C001646
品系全称
C57BL/6JCya-Rhotm3(hRHO)/Cya
品系背景
C57BL/6JCya
品系状态
使用本品系发表的文献需注明： B6-hRHO (Promoter) mice (Catalog C001646) were purchased from Cyagen.
交付类型
周龄
性别
基因型
数量
品系介绍
视网膜色素变性（Retinitis Pigmentosa, RP）是一种遗传性视网膜疾病，全球患病率约为1:5000-1:3000。RP具有很大的临床和遗传异质性，视紫红质基因（Rhodopsin, RHO）突变导致约25％的显性RP [1]。RHO编码的视紫红蛋白与视觉光传导和GPCR下游信号密切相关，视紫红蛋白在视觉形成过程中光信号的传导至关重要，大多数RHO突变导致视紫红蛋白在感光细胞中高水平表达，使得大量的突变蛋白在细胞中定位异常并聚集，造成感光细胞凋亡，不能行使正常的光信号传导功能。此外，RHO基因的突变也与先天性静止性夜盲（CSNB）有关 [2-4]。目前靶向RHO基因以治疗视网膜色素变性的基因疗法有ASO、CRISPR等，全人源化动物模型的应用有助于推动RHO相关潜在疗法向临床试验进一步转化 [5-10]。
本模型为小鼠Rho基因人源化模型，利用基因编辑技术将小鼠内源性Rho基因替换为对应的人源RHO基因片段，以在小鼠体内表达人源的视紫红蛋白。在该模型中，小鼠Rho基因被人源RHO基因取代，人源基因编码的蛋白在小鼠体内正常表达，因此该模型的视网膜外形和功能和野生型小鼠相同，不存在视觉缺陷。该模型可用于视觉信号传导和视网膜色素变性（RP）的研究。此外，基于自主研发的TurboKnockout融合BAC重组的技术创新，赛业生物还可提供基于该模型构建的热门点突变疾病模型，也可针对不同点突变提供定制服务，以满足广大研发人员关于视网膜色素变性（RP）疾病的药效学等实验需求。
参考文献
Hartong, D. T., Berson, E. L., & Dryja, T. P. (2006). Retinitis pigmentosa. The Lancet, 368(9549), 1795-1809.
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.
构建方案
图1. B6-hRHO (Promoter)小鼠基因编辑策略。将小鼠Rho基因5'UTR上游至3'UTR下游的序列替换为人源RHO基因5'UTR上游至3'UTR下游的序列。
