Retinoblastoma, a childhood eye cancer, has the root cause of biallelic inactivation of the RB1 tumor suppressor gene. Protheragen, a leading provider of rare disease drug and therapy development services, specializes in creating sophisticated animal models that closely mimic the human disease, facilitating robust preclinical research and therapeutic evaluation.
Overview of Retinoblastoma Animal Models
Retinoblastoma animal models are experimental systems designed to replicate the genetic and phenotypic characteristics of human retinoblastoma. These models are crucial for understanding the disease's molecular mechanisms, identifying potential therapeutic targets, and evaluating the efficacy and safety of new treatments. By providing a controlled environment to study tumor development and response to therapy, these models bridge the gap between in vitro studies and clinical trials, accelerating the drug discovery process.
Fig.1 Workflow for tumor sampling and genomic and pharmacological characterization. (Schaiquevich P.,
et al., 2022)
Types of Retinoblastoma Animal Models
- Genetically Engineered Mouse Models (GEMMs)
GEMMs involve the targeted manipulation of genes implicated in retinoblastoma, such as Rb1, p107, and p53. These models are created using Cre-Lox technology, where specific genes are deleted or mutated in retinal progenitor cells, leading to tumor formation.
Table 1. Genetically engineered mouse models of retinoblastoma (RB). (Schaiquevich P., et al., 2022)
| Genotype of the Genetically Engineered Mouse Model |
Characteristics |
Study Objective |
| Rb1/p107 DKO |
68% of mice with RB develop by 280 days, and 22% of mice carry bilateral RB |
Additional genes required in cooperation with pRb loss for tumorigenesis and early RB |
| Rb1/p130 DKO |
85% of mice with RB develop by 128 days, and 28% of mice carry bilateral RB |
Early and advanced RB |
| Rb1/p107/p130 TKO |
100% of mice with RB develop by 80 days, and 83% of mice carry bilateral RB |
Very aggressive RB |
| Rb1/p107/p53 TKO |
98–100% of mice with RB develop by 100 days, and 65% of mice carry bilateral RB |
Advanced and aggressive RB |
| Rb1/p107 DKO/MDMX Tg |
90% of mice with RB and 63% of mice carry bilateral RB |
Advanced and aggressive RB |
| Rb1/p107/Pten TKO |
100% of mice with bilateral RB develop by 30 days |
Tumor progression related to the PI3K/AKT pathway |
| Rb1 KO/MYCN |
100% of mice with RB develop by 54 days |
Oncogenic effects of MYCN on RB |
Xenograft models are created by transplanting human retinoblastoma cells or tissue into an animal host, typically an immunodeficient mouse. This approach bypasses the time-consuming process of genetic engineering and allows for the rapid establishment of tumors.
Key Features: Xenograft models are particularly valuable for high-throughput drug screening and efficacy testing. They provide a platform to evaluate the anti-tumor effects of various compounds on established human cell lines. The use of orthotopic xenografts, where cells are injected into the rodent eye, more accurately mimics the intraocular environment of human disease.
Our Services
At Protheragen, we understand that effective preclinical research hinges on the quality and relevance of the animal models used. Our services are designed to address the specific needs of our clients, offering tailored solutions for every stage of drug development. We leverage our deep biological expertise and state-of-the-art facilities to construct models that precisely simulate the initiation, progression, and metastatic characteristics of human retinoblastoma.
Protheragen offers retinoblastoma animal model development services, featuring anterior chamber/vitreous injection and subretinal injection methods. We provide well-characterized retinoblastoma cell lines such as Y79, WERI, and SO-RB50 for transplantation. These services are ideal for studying tumor growth, metastasis, and therapeutic efficacy in relevant ocular environments.
Anterior Chamber/Vitreous Injection
Tumor cells injected into the anterior chamber or vitreous cavity of nude mice show rapid growth, with opacity visible within 3 days, gray-white tumor masses by day 6, corneal opacity by day 9, and protrusion of the eyeball by day 12, accompanied by destruction of intraocular structures.
Subretinal Injection
Tumor cells injected subretinally form floating tumor masses in the vitreous cavity by 3 weeks, leading to the destruction of eyeball structures and protrusion of solid tumors by 4 weeks. Nude mice exhibit significant weight loss by 5 weeks post-injection.
Protheragen provides custom genetic knockout models using state-of-the-art gene editing technologies. Our team of experts can create models with precise genetic modifications to mimic specific mutations associated with retinoblastoma. These models are designed to provide a robust platform for studying disease mechanisms and evaluating targeted therapies.
| Model Types |
Conditional Knockout Mice |
| Model Name |
Rbl2-Flox Mice |
| Also Known As |
C57BL/6-Rbl2tm1(flox)
|
| Detailed Description |
These mice feature loxP sites flanking Exon 2 of the Rbl2 gene. Upon mating with a Cre recombinase-expressing strain, this model enables tissue-specific conditional knockout of the Rbl2 gene. |
| NCBI ID |
19651 |
| MGI ID |
105085 |
| Gene Alias |
Rb2, PRB2, p130, RBR-2 |
| Sales Status |
Sperm cryopreservation |
| Applications & Therapeutic Areas |
Cancer research |
| Ensembl ID |
ENSMUSG00000031666 |
| Pubmed |
Rbl2 |
| Human Ortholog |
RBL2 |
Case Study
Protheragen has successfully developed a Nude Mouse Ectopic Xenograft Model for retinoblastoma research using Balb/c Nude mice and the WERI-Rb-1 cell line. The tumor progression and average body weight changes of the mice were monitored using IVIS, confirming the successful establishment of the retinoblastoma animal model.
Fig 2. The tumor progression curve and the average weight change curve of the mice during the IVIS monitoring period.
The combination of genetic and xenograft models, coupled with Protheragen's profound expertise in ocular oncology, provides an unparalleled platform for understanding retinoblastoma tumor biology. By partnering with Protheragen, researchers can access the tools and expertise required to accelerate the discovery and development of life-saving therapies for children afflicted with this disease. If you are interested in our services, please feel free to
contact us.
References
- Schaiquevich, Paula, et al. "Treatment of retinoblastoma: what is the latest and what is the future." Frontiers in Oncology 12 (2022): 822330.
- Kaewkhaw, Rossukon, and Duangnate Rojanaporn. "Retinoblastoma: etiology, modeling, and treatment." Cancers 12.8 (2020): 2304.
- Nair, Rohini M., Swathi Kaliki, and Geeta K. Vemuganti. "Animal models in retinoblastoma research." Saudi Journal of Ophthalmology 27.3 (2013): 141-146.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
