PMID- 10653000
OWN - NLM
STAT- MEDLINE
DCOM- 20000217
LR  - 20191103
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 80
IP  - 1
DP  - 2000 Jan
TI  - Docosahexaenoic acid deficit is not a major pathogenic factor in
      peroxisome-deficient mice.
PG  - 31-5
AB  - Docosahexaenoic acid (DHA), a major component of membrane phospholipids in brain 
      and retina, is profoundly reduced in patients with peroxisome biogenesis
      disorders (Zellweger syndrome). Supplementing newborn patients with DHA resulted 
      in improved muscular tone and visual functions. The purpose of this study was to 
      investigate (a) whether DHA levels were also reduced in newborn PEX5 knockout
      mice, the mouse model of Zellweger syndrome that we recently generated; (b)
      whether these levels could be normalized by supplying DHA; and (c) whether this
      results in longer survival. The DHA concentration in brain of newborn PEX5-/-
      mice was reduced by 40% as compared with levels in normal littermates; in liver, 
      no differences were noticed. The daily administration of 10 mg of DHA-ethyl ester
      (EE) to pregnant heterozygous mothers during the last 8 days of gestation
      resulted in a normalization of brain DHA levels in Zellweger pups. However, no
      clinical improvement was observed in these pups, and the neuronal migration
      defect was unaltered. These data suggest that the accretion of DHA in the brain
      at the end of embryonic development is not only supported by the maternal supply 
      but also depends on synthesis in the fetal brain. Furthermore, the DHA deficit
      does not seem to be a major pathogenic factor in the newborn Zellweger mice.
FAU - Janssen, A
AU  - Janssen A
AD  - Laboratory of Clinical Chemistry, Faculty of Pharmaceutical Sciences, K.U.
      Leuven, Belgium. Myriam.Baes@uz.kuleuven.ac.be
FAU - Baes, M
AU  - Baes M
FAU - Gressens, P
AU  - Gressens P
FAU - Mannaerts, G P
AU  - Mannaerts GP
FAU - Declercq, P
AU  - Declercq P
FAU - Van Veldhoven, P P
AU  - Van Veldhoven PP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (PEX5 protein, human)
RN  - 0 (Peroxisome-Targeting Signal 1 Receptor)
RN  - 0 (Pex5 protein, mouse)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 25167-62-8 (Docosahexaenoic Acids)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Chromatography, Gas
MH  - Disease Models, Animal
MH  - Docosahexaenoic Acids/administration & dosage/*metabolism
MH  - Female
MH  - Heterozygote
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Peroxisome-Targeting Signal 1 Receptor
MH  - Pregnancy
MH  - Receptors, Cytoplasmic and Nuclear/genetics
MH  - Zellweger Syndrome/*metabolism
EDAT- 2000/02/01 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/02/01 09:00
PHST- 2000/02/01 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/02/01 09:00 [entrez]
AID - 10.1038/labinvest.3780005 [doi]
PST - ppublish
SO  - Lab Invest. 2000 Jan;80(1):31-5. doi: 10.1038/labinvest.3780005.