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DOI: 10.1055/s-0029-1240101
Proteomic genotyping in a mouse model of trait anxiety exposes disease relevant pathways
Brain proteome analysis of mice selectively bred for either high or low anxiety-related behavior revealed quantitative and qualitative protein expression differences. Enolase phosphatase was identified as a protein that shows a different mobility during twodimensional gel electrophoresis. The altered electrophoretic behavior is now identified to be caused by two single nucleotide polymorphisms. In both cases the genetic polymorphism introduces an amino acid change in protein sequence resulting in differenzial mobility on SDS gels. This was demonstrated by recombinantly expressing the two enolase phosphatase isoforms. Functional studies indicate that the enolase phosphatase isoform from the high anxiety mouse line has a lower enzymatic activity than its low anxiety mouse counterpart. Enolase phosphatase is a member of the methionine salvage pathway which is responsible for the synthesis of S-adenosyl-L-methionine, a natural compound with potential antidepressant activities. In addition, it is linked to the polyamine pathway whose members have functions in anxiety/depression-related behaviors. In a freely-segregating F2 panel, both single nucleotide polymorphisms were significantly associated with locomotion-independent trait anxiety. The presence of this protein marker in white blood cells creates the opportunity to screen for its expression in clinical blood specimens from patients suffering from anxiety.