Pex7-flox Mouse

Pex7, a shuttling receptor, is crucial for transporting matrix proteins with a type 2 peroxisomal targeting signal (PTS2) to peroxisomes [3,4,6]. Peroxisomes are involved in various metabolic processes like lipid processing, reactive oxygen detoxification, and play a role in maintaining cellular redox homeostasis [2,5]. Pex7-mediated PTS2 protein import contributes to fatty acid β-oxidation, glucose metabolism in fungi, and is also associated with cadmium-induced ROS and auxin homeostasis in plants [2,3].

In a Pex7 deficient mouse series, different genotypes (homozygous for hypomorphic allele, compound heterozygous, or homozygous for null allele) led to a graded reduction in plasmalogen (Pls) and increases in C26:0-LPC and phytanic acid (PA) in plasma and brain. These mice showed loss of cerebellar Purkinje cells, decrease in brain myelin basic protein, hyperactive behavior, and reduction in brain neurotransmitters (dopamine, norepinephrine, serotonin, and GABA), indicating a genotype-phenotype correlation in Rhizomelic chondrodysplasia punctata type 1 (RCDP1) [1].

In conclusion, Pex7 is essential for the import of PTS2-containing proteins to peroxisomes, influencing various metabolic and cellular processes. The Pex7 deficient mouse models have provided insights into the pathophysiology of RCDP1, highlighting the role of Pex7 in this disease and its associated biochemical and neurobehavioral phenotypes [1].