Prenatal and postnatal development of peroxisomal lipid-metabolizing pathways in the mouse

The ontogeny of the following peroxisomal metabolic pathways was evaluated in mouse liver and brain: alpha -oxidation, beta -oxidation and ether phosp holipid synthesis. In mouse embryos lacking functional peroxisomes (PEX5(-/ -) knock-out), a deficiency of plasmalogens and an accumulation of the very -long-chain fatty acid C-26:0 was observed in comparison with control litte rmates, indicating that ether phospholipid synthesis and beta -oxidation ar e already active at mid-gestation in the mouse. Northern analysis revealed that the enzymes required for the beta -oxidation of straight-chain substra tes are present in liver and brain during embryonic development but that th ose responsible for the degradation of branched-chain substrates are presen t only in liver from late gestation onwards. The expression pattern of tran scripts encoding enzymes of the alpha -oxidation pathway suggested that alp ha -oxidation is initiated in the liver around birth and is not active in b rain throughout development. Remarkably, a strong induction of the mRNA lev els of enzymes involved in alpha -oxidation and beta -oxidation was observe d around birth in the liver. In contrast, enzyme transcripts that were expr essed in brain were present at rather constant levels throughout prenatal a nd postnatal development. These results suggest that the defective ether ph ospholipid synthesis and/or peroxisomal beta -oxidation of straight-chain f atty acids might be involved in the pathogenesis of the prenatal organ defe cts in peroxisome-deficient mice and men.