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Byron C. Jones
Quantitative Genetic Analysis of Ventral Midbrain and Liver Iron in BXD Recombinant Inbred Mice
Male and female mice from15 of the BXD/Ty recombinant
inbred strain panel were examined for regional brain and
liver iron content. Brain regions included medial prefrontal
cortex, nucleus accumbens, caudate-putamen and
ventral midbrain. Our focal tissue was the ventral
midbrain, containing the ventral tegmentum and substantia
nigra. This area contains the perikarya of the
dopamine neurons that project to nucleus accumbens and
caudate-putamen. Genetic correlations between ventral
midbrain and liver iron content were not statistically
significant, suggesting that peripheral and central iron
regulatory systems are largely independent. Correlations
between ventral midbrain iron and iron in the caudateputamen
and nucleus accumbens, but not the prefrontal
cortex were moderately high and significant. Ventral
midbrain and liver iron contents were subjected to
quantitative trait loci analysis to identify associated
chromosomal locations. This analysis revealed several
suggestive loci for iron content in ventral midbrain but
fewer loci for liver. Genetic correlations between ventral
midbrain iron and published dopamine functional indices
were significant, suggesting a link between ventral
midbrain iron status and central dopamine neurobiology.
This work shows the value of quantitative genetic analysis
in the neurobiology of iron and in showing the close
association between ventral midbrain iron and nigrostriatal/
mesolimbic dopamine function.
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