Mouse Models with Peroxisome Biogenesis Defects

Peroxisomes are ubiquitous organelles in mammalian cells but it is still unclear how they contribute to normal development and tissue homeostasis. To address this question, gene targeting techniques have been applied on several peroxins to interfere with peroxisome biogenesis in mice. Both peroxins involved in peroxisomal matrix import and peroxins necessary for peroxisome division were inactivated. Besides generalized knockouts, mice were created with conditional inactivation of PEX genes either in certain cell types or induced in adulthood. Defective matrix import generates empty peroxisomal ghosts and metabolic derangements that are a direct consequence of peroxisome inactivity. In addition, ablation of functional peroxisomes from hepatocytes affects other cellular compartments such as mitochondria and the endoplasmic reticulum. Peroxisome inactivity in the central nervous system causes both developmental and degenerative pathologies. The impairment of peroxisome division in mice also results in cerebral and hepatic pathologies although peroxisomal metabolites are unaffected.