Antioxidant enzyme, 3-mercaptopyruvate sulfurtransferase-knockout mice exhibit increased anxiety-like behaviors: a model for human mercaptolactate-cysteine disulfiduria

• Published in: Scientific reports 2013-06, Vol.3 (1), p.1986-1986, Article 1986
• Main Authors: Nagahara, Noriyuki, Nagano, Masatoshi, Ito, Takaaki, Shimamura, Kenji, Akimoto, Toshio, Suzuki, Hidenori
• Format: Article
• Language: English
• Subjects: 3-Mercaptopyruvate sulfurtransferase; 631/378/1689/1300; 631/61/17/1511; 692/420; 692/699/317; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Metabolism, Inborn Errors - metabolism; Animal models; Animals; Antioxidants; Anxiety; Anxiety - genetics; Behavior, Animal; Biogenic Monoamines - metabolism; Cysteine; Disease Models, Animal; Embryo cells; Female; Gene Expression; Gene Order; Gene Targeting; Heterozygote; Hippocampus - metabolism; Hippocampus - pathology; Homeostasis; Homozygote; Humanities and Social Sciences; Humans; Male; Mice; Mice, Knockout; multidisciplinary; Prefrontal cortex; Receptor, Serotonin, 5-HT1A - genetics; Receptor, Serotonin, 5-HT1A - metabolism; Rodents; Science; Serotonin; Stem cell transplantation; Stem cells; Sulfurtransferase; Sulfurtransferases - genetics; Sulfurtransferases - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep01986

Human mercaptolactate-cysteine disulfiduria (MCDU) was first recognized and reported in 1968. Most cases of MCDU are associated with mental retardation, while the pathogenesis remains unknown. To investigate it, we generated homozygous 3-mercaptopyruvate sulfurtransferase (MST: EC 2.8.1.2) knockout (KO) mice using C57BL/6 embryonic stem cells as an animal model. The MST-KO mice showed significantly increased anxiety-like behaviors with an increase in serotonin level in the prefrontal cortex (PFC), but not with abnormal morphological changes in the brain. MCDU can be caused by loss in the functional diversity of MST; first, MST functions as an antioxidant protein. MST possessing 2 redox-sensing molecular switches maintains cellular redox homeostasis. Second, MST can produce H 2 S (or HS − ). Third, MST can also produce SO x . It is concluded that behavioral abnormality in MST-KO mice is caused by MST function defects such as an antioxidant insufficiency or a new transducer, H 2 S (or HS − ) and/or SO x deficiency.