Mouse Models to Study Peroxisomal Functions and Disorders: Overview, Caveats, and Recommendations

Area of Science:

• Biochemistry
• Genetics
• Cell Biology

Background:

• Peroxisomal disorders are a group of genetic diseases affecting metabolism.
• Mouse models are crucial for studying peroxisomal function and disease.
• Significant advancements in creating diverse mouse models have occurred over the past three decades.

Purpose of the Study:

• To provide a comprehensive overview of available mouse models with deficiencies in peroxisomal functions.
• To characterize the methodologies used for generating these mouse models (global, hypomorph, cell type selective, inducible, knockin).
• To discuss the relevance of these models in mimicking human pathologies and the challenges in their application.

Main Methods:

• Review of existing literature on peroxisomal mouse models.
• Categorization of models based on genetic modification strategies.
• Analysis of phenotypic outcomes and their correlation with human diseases.
• Discussion of methods for validating loss-of-function in peroxisomal proteins.

Main Results:

• A wide array of mouse models with impaired peroxisomal functions have been developed using various genetic approaches.
• Some models accurately reflect human peroxisomal diseases, while others show limited or no human counterpart.
• Phenotypic manifestation in some mouse models necessitates specific dietary interventions for clear observation.
• Different strategies are employed to validate the loss-of-function depending on the targeted peroxisomal protein.

Conclusions:

• The diversity of peroxisomal mouse models offers valuable tools for research, but careful consideration of their limitations is essential.
• Translating findings from mouse models to human peroxisomal disorders requires understanding model-specific characteristics and potential compensatory mechanisms.
• Further refinement of mouse models and validation techniques will enhance their utility in understanding and treating peroxisomal diseases.