In Vivo Model Development for Stargardt Disease

Protheragen offers comprehensive in vivo animal model development services specifically tailored for Stargardt disease research and preclinical drug evaluation. Leveraging our extensive expertise in genetic engineering and translational ophthalmology, we provide a suite of validated animal models that accurately recapitulate the key pathological features of Stargardt disease, enabling efficient and reliable assessment of novel therapeutics.

Stargardt disease, the most common form of inherited juvenile macular degeneration, is primarily caused by mutations in the ABCA4 gene, leading to progressive vision loss. Animal models are indispensable for elucidating disease mechanisms and evaluating potential treatments. At Protheragen, we utilize a range of genetically engineered Mus musculus (mouse) models—including various strains such as 129S-Abca4tm1Ght/J, 129S4/SvJae-Abca4tm1gbt, 129Sv x C57BL/6J, and Balb/c—as well as a conditional knockout Sus scrofa (pig) model. These models feature targeted knockouts of the Abca4 gene, with some also incorporating Rdh8 deletions, closely mirroring the genetic and phenotypic characteristics of human Stargardt disease. The inclusion of both rodent and large animal models ensures translational relevance and flexibility for diverse research needs.

Genetic Knockout Models

These models are created by targeted deletion or mutation of the Abca4 gene, which is the principal genetic cause of Stargardt disease in humans. Utilizing advanced gene targeting and CRISPR/Cas9 technologies, we offer multiple mouse strains (e.g., 129S-Abca4tm1Ght/J, 129S4/SvJae-Abca4tm1gbt, Balb/c, and mixed backgrounds) and a conditional knockout pig model. Key advantages include high construct validity, reproducibility, and the ability to study disease onset and progression in a controlled genetic context. These models are ideal for studying pathophysiology, biomarker discovery, and preclinical efficacy of gene therapies, small molecules, and other interventions.

Double Knockout Models

This model type involves simultaneous knockout of both Abca4 and Rdh8 genes in mice, further exacerbating retinal pathology and accelerating disease progression. The dual knockout approach mimics more severe or complex forms of retinal degeneration, providing a robust platform for evaluating therapies targeting advanced or multifactorial disease states. Advantages include enhanced sensitivity for detecting treatment effects and the ability to model synergistic genetic interactions. Applications encompass testing of combination therapies, mechanistic studies, and validation of therapeutic targets.

Conditional Knockout Large Animal Models

Our conditional knockout Sus scrofa (pig) model enables tissue-specific and temporally controlled inactivation of the ABCA4 gene. Pigs offer anatomical and physiological similarities to the human eye, including comparable retinal structure and size, which enhances translational value for late-stage preclinical studies. The conditional approach allows for precise modeling of disease onset and progression, and for evaluating the safety and efficacy of localized interventions. This model is particularly advantageous for pharmacokinetic studies, surgical device testing, and large-scale imaging or functional assessments.

Protheragen delivers a complete solution for Stargardt disease model development and utilization, encompassing model design, generation, colony management, phenotypic validation, and customized study execution. Key efficacy endpoints include retinal morphology (via OCT and histology), visual function (ERG, optokinetic tracking), lipofuscin accumulation, photoreceptor cell death, and molecular biomarker quantification. Our analytical capabilities span advanced imaging, quantitative PCR, immunohistochemistry, and next-generation sequencing. Rigorous quality control is ensured at every stage, with genotypic confirmation, standardized phenotyping protocols, and adherence to ethical and regulatory standards.

Partnering with Protheragen provides access to a dedicated team of ophthalmic model experts, a diverse portfolio of validated Stargardt disease models, and end-to-end support from model selection to data interpretation. Our commitment to scientific excellence and client collaboration ensures that your research objectives are met with precision, reliability, and translational impact. Contact us today to discuss your project needs and accelerate your Stargardt disease therapeutic development.