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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300451-JLR200 on April 21, 2004

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Journal of Lipid Research, Vol. 45, 1272-1278, July 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Characterization of apoM in normal and genetically modified mice

Kirsten Faber*, Olof Axler*, Björn Dahlbäck1,* and Lars Bo Nielsen1,*,{dagger}

* Division of Clinical Chemistry, Department of Laboratory Medicine, University of Lund, University Hospital Malmö, S-20502 Malmö, Sweden
{dagger} Department of Clinical Biochemistry, Rigshospital, University of Copenhagen, Copenhagen DK-2100, Denmark

1 To whom correspondence should be addressed. e-mail: larsbo{at}rh.dk (L.B.N.); bjorn.dahlback{at}klkemi.mas.lu.se (B.D.)

A novel human apolipoprotein [apolipoprotein M (apoM)] was recently described and demonstrated to be a lipocalin. We have now examined apoM in wild-type mice and mice with genetically altered lipoprotein metabolism. Liver and kidney showed high mRNA expression, whereas spleen, heart, brain, and testis demonstrated low expression. ApoM gene expression was initiated on embryonic day 10. Western blot analysis of plasma suggested that mouse apoM, like its human counterpart, is secreted with a retained signal peptide, but unlike human apoM it is not glycosylated. Gel filtration of plasma showed apoM to be associated with HDL-sized particles in wild-type and apoA-I-deficient mice and with HDL- and LDL-sized particles in LDL receptor-deficient mice, whereas apoM was mainly found in VLDL-sized particles in high-fat, high-cholesterol-fed apoE-deficient mice. The plasma concentration of apoM was similar in wild-type, LDL receptor-deficient, and apoE-deficient mice but was reduced to 33% in apoA-I-deficient compared with wild-type mice (P = 0.007).

These data suggest that apoM mainly associates with HDL in normal mice but also with the pathologically increased lipoprotein fraction in genetically modified mice. The substantially decreased apoM levels in apoA-I-deficient mice suggest a connection between apoM and apoA-I metabolism.

Supplementary key words apolipoprotein A-I • apolipoprotein M • high density lipoprotein • low density lipoprotein • very low density lipoprotein


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