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A Mouse Model System to Study Peroxisomal Roles in Neurodegeneration of Peroxisome Biogenesis Disorders
Yuichi Abe1, Shigehiko Tamura1, Masanori Honsho2
1Faculty of Arts and Science, Kyushu University, Fukuoka, Japan.
Insights
Mouse models of peroxisome biogenesis disorders (PBDs) reveal neurodegenerative symptoms and metabolic issues. These PBD models highlight the role of interorgan and intercellular communication in disease pathogenesis.
Area of Science:
- Genetics
- Neuroscience
- Cell Biology
Background:
- Peroxisome biogenesis disorders (PBDs) are genetic conditions causing neurodegeneration, including neuronal migration defects and cerebellar malformations.
- Fourteen PEX genes are known to cause PBDs, impacting cellular function and organismal health.
Purpose of the Study:
- To investigate the molecular mechanisms underlying PBD pathogenesis.
- To provide an overview of Pex-inactivated mouse phenotypes and current understanding of PBDs.
Main Methods:
- Generation of Pex-knockout mouse models through targeted gene disruption.
- Development of tissue- or cell type-specific Pex gene inactivation using the Cre-loxP system.
Main Results:
- Pex-knockout mice exhibit pathological phenotypes and metabolic abnormalities mirroring human PBD patients.
- Genetically modified mice demonstrate that PBD phenotypes are influenced by interorgan and intercellular communication.
Conclusions:
- Mouse models are valuable tools for studying PBD pathogenesis.
- Further research is needed to fully elucidate the mechanistic insights into PBD pathogenesis.
Abstract:
Fourteen PEX genes are currently identified as genes responsible for peroxisome biogenesis disorders (PBDs). Patients with PBDs manifest as neurodegenerative symptoms such as neuronal migration defect and malformation of the cerebellum. To address molecular mechanisms underlying the pathogenesis of PBDs, mouse models for the PBDs have been generated by targeted disruption of Pex genes. Pathological phenotypes and metabolic abnormalities in Pex-knockout mice well resemble those of the patients with PBDs. The mice with tissue- or cell type-specific inactivation of Pex genes have also been established by using a Cre-loxP system. The genetically modified mice reveal that pathological phenotypes of PBDs are mediated by interorgan and intercellular communications. Despite the illustrations of detailed pathological phenotypes in the mutant mice, mechanistic insights into pathogenesis of PBDs are still underway. In this chapter, we overview the phenotypes of Pex-inactivated mice and the current understanding of the pathogenesis underlying PBDs.
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