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Manipulation of brain iron status in two mutant mouse models: effects on myelin
Author(s) -
Connor J. R.,
Thompson K.,
Ortiz E.,
Pasquini J. M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.16_5.x
Subject(s) - myelin , galactolipids , ferritin , proteolipid protein 1 , transferrin , galactolipid , oligodendrocyte , biochemistry , biology , myelin basic protein , metabolism , endocrinology , phospholipid , medicine , chemistry , central nervous system , gene , chloroplast , membrane
A number of observations point to iron as an essential factor in myelination and oligodendrocyte biology. However, the specific role of iron in myelin production and maintenance is not known. This role could be as an essential co‐factor, as a transcriptional or translational regulator or a metabolic fuel. We introduce two animal models each with a unique defect in iron metabolism to begin to dissect the role of iron in myelin production. One of the animal models, the hypotransferrinemic (hpx) mouse, lacks the ability to make transferrin. This animal represents a model of compromised ability to mobilize iron within oligodendrocytes. The other animal model is a heterozygote for a null mutation in H‐ferritin the iron storage protein. Thus these oligodendrocytes have limited capacity to store iron. In the hpx mice, the total myelin protein concentration is decreased by 20% ( p < 0.05) and the galactolipid content is decreased by 21% ( p < 0.05), whereas the phospholipid content was unchanged. CNPase and PLP were significantly higher in the wild type controls compared to the hpx mice, but MBP18 and MBP17 were higher in the hpx mice. The decrease in H‐ferritin expression was associated with a 22% decrease in myelin proteins with only the decrease in PLP reaching statistical significance among the individual proteins. The galactolipids decreased by 20% but there was no significant difference in the phospholipids. These data demonstrate that compromised iron status has a selective effect on galactolipids but not phospholipids in myelin. The protein content of myelin is also altered, but there are specific changes in myelin protein content based on the type of change in iron metabolism.