Proteomic-based genotyping in a mouse model of trait anxiety exposes disease-relevant pathways

被引：24

作者：

Ditzen, C. ^{[1
]}

Varadarajulu, J. ^{[1
]}

Czibere, L. ^{[1
]}

Gonik, M. ^{[1
]}

Targosz, B. S. ^{[1
]}

Hambsch, B. ^{[1
]}

Bettecken, T. ^{[1
]}

Kessler, M. S. ^{[1
]}

Frank, E. ^{[1
]}

Bunck, M. ^{[1
]}

Teplytska, L. ^{[1
]}

Erhardt, A. ^{[1
]}

Holsboer, F. ^{[1
]}

Mueller-Myhsok, B. ^{[1
]}

Landgraf, R. ^{[1
]}

Turck, C. W. ^{[1
]}

机构：

[1] Max Planck Inst Psychiat, D-80804 Munich, Germany

来源：

MOLECULAR PSYCHIATRY | 2010年 / 15卷 / 07期

关键词：

trait anxiety; biomarker; enolase phosphatase; metabolic pathways; ADENOSYL-L-METHIONINE; MAJOR DEPRESSION; GLYOXALASE-I; SERUM FOLATE; FOLIC-ACID; MICE; POLYAMINES; DISORDERS; BEHAVIOR; BRAIN;

D O I：

10.1038/mp.2008.146

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In our biomarker identification efforts, we have reported earlier on a protein that differs in its electrophoretic mobility between mouse lines bred either for high or low trait anxiety. The altered electrophoretic behavior of enolase phosphatase (EP) is now identified to be caused by two single-nucleotide polymorphisms. In both cases, the genetic polymorphism introduces an amino acid change in the protein's sequence resulting in differential mobility on SDS gels. This was shown by recombinantly expressing the two EP isoforms. Functional studies indicate that the EP isoform from the high anxiety mouse line has a lower enzymatic activity than does its low anxiety mouse counterpart. EP is a member of the methionine salvage pathway that 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, further supporting a functional role of EP for this phenotype. The study shows that proteomic analysis can reveal genotypic differences relevant for the phenotype. The identified protein alterations, in turn, can expose metabolic pathways pertinent to the behavioral phenotype. Molecular Psychiatry (2010) 15, 702-711; doi:10.1038/mp.2008.146; published online 13 January 2009

引用

页码：702 / 711

页数：10

共 35 条

[1]

[Anonymous], WORLD J BIOL PSYCHIA

[2] Test- and behavior-specific genetic factors affect WKY hypoactivity in tests of emotionality [J].