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 phospholipid 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 littermates, indicating that ether phospholipid synthesis and beta-oxidation are already active at mid-gestation in the mouse. Northern analysis revealed that the enzymes required for the beta-oxidation of straight-chain substrates are present in liver and brain during embryonic development but that those responsible for the degradation of branched-chain substrates are present only in liver from late gestation onwards. The expression pattern of transcripts encoding enzymes of the alpha-oxidation pathway suggested that alpha-oxidation is initiated in the liver around birth and is not active in brain throughout development. Remarkably, a strong induction of the mRNA levels of enzymes involved in alpha-oxidation and beta-oxidation was observed around birth in the liver. In contrast, enzyme transcripts that were expressed in brain were present at rather constant levels throughout prenatal and postnatal development. These results suggest that the defective ether phospholipid synthesis and/or peroxisomal beta-oxidation of straight-chain fatty acids might be involved in the pathogenesis of the prenatal organ defects in peroxisome-deficient mice and men.
Huyghe
S
S
Laboratorium Klinische Chemie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Campus Gasthuisberg O/N, B 3000 Leuven, Belgium.
Casteels
M
M
Janssen
A
A
Meulders
L
L
Mannaerts
G P
GP
Declercq
P E
PE
Van Veldhoven
P P
PP
Baes
M
M
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000201:enzymology / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011247:Pregnancy
D010743:Phospholipids