In Vivo Model Development for Leber Hereditary Optic Neuropathy

Protheragen offers comprehensive in vivo animal model development services for Leber hereditary optic neuropathy (LHON), supporting preclinical research and therapeutic evaluation. Our expertise in generating and utilizing validated mouse models enables researchers to investigate disease mechanisms and assess the efficacy of novel interventions for LHON with scientific rigor and translational relevance.

Leber hereditary optic neuropathy is a mitochondrial disorder characterized by acute or subacute loss of central vision, primarily affecting young adults. Animal models, particularly those based on Mus musculus (mouse), are essential tools for elucidating LHON pathophysiology and evaluating potential treatments. Protheragen employs widely used strains such as C57BL/6, C57BL/6J, and DBA/1J, incorporating both transgenic and knockout approaches targeting mitochondrial genes like ND4, ND1, and Ndufs4. These models closely mimic key features of human LHON, including retinal ganglion cell degeneration and mitochondrial dysfunction, thereby providing robust platforms for translational research.

Genetic Models

Genetic models are established by introducing specific mutations or transgenes associated with LHON into the mouse genome. Protheragen offers transgenic lines expressing mutant human ND4 or ND1 genes, as well as Ndufs4 knockout models. These models faithfully recapitulate the mitochondrial dysfunction and retinal ganglion cell loss observed in LHON patients. Key advantages include stable inheritance, reproducibility, and the ability to study disease progression and therapeutic interventions over time. Primary applications include mechanistic studies, drug efficacy testing, and evaluation of gene therapy approaches.

Conditional/Cell Type-Specific Models

Conditional or cell type-specific models utilize Cre-lox or similar systems to drive gene expression or knockout in targeted cell populations, such as retinal ganglion cells. For example, Protheragen provides retinal ganglion cell-specific ND1 transgenic models on the DBA/1J background. This approach enables precise investigation of LHON pathogenesis within the most affected neuronal populations, reducing off-target effects and improving translational value. These models are ideal for dissecting cell-autonomous disease mechanisms and for testing targeted therapeutics.

Knockout Models

Knockout models involve the complete or partial inactivation of endogenous genes critical for mitochondrial function, such as Ndufs4. These models exhibit mitochondrial respiratory chain deficiencies and optic neuropathy phenotypes similar to LHON. Their advantages include the ability to model loss-of-function mutations and to study compensatory biological responses. Knockout mice are used extensively for validating genetic targets, exploring disease-modifying pathways, and assessing the impact of therapeutic interventions.

Protheragen delivers a full-spectrum animal model development service for LHON, encompassing custom model generation, colony management, and in vivo efficacy studies. Our service includes phenotypic characterization, visual function assessments (e.g., optokinetic response, electroretinography), histopathological analysis of retinal ganglion cells, mitochondrial function assays, and molecular profiling. Analytical capabilities extend to next-generation sequencing, quantitative PCR, immunohistochemistry, and biochemical assays for oxidative stress and apoptosis. Stringent quality control measures, including genotyping, health monitoring, and standardized experimental protocols, ensure reliable and reproducible results for your research.

Partnering with Protheragen provides access to scientifically validated LHON animal models, expert technical support, and comprehensive analytical services tailored to your research objectives. Our commitment to quality, innovation, and client collaboration accelerates the development of effective therapies for LHON. Contact us today to discuss your project needs and learn how our in vivo model solutions can advance your LHON research.