title: Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat.
abstract: Selenoprotein is associated with a variety of serious diseases, including infectious diseases, neurodegenerative disorders, cancer and cardiovascular disease. The aim of this study was to produce a new transgenic (Tg) rat expressing human selenoprotein M (SelM) in order to examine the protective function of the antioxidant status in vivo. To achieve this, a new lineage of Tg rats was produced by the microinjection of pCMV/GFP-hSelM constructs into a fertilized rat egg. Several conclusions can be drawn based on the results of the present study. The human SelM gene was successfully expressed at both the transcription and protein levels in the CMV/GFP-hSelM Tg rats. This Tg rat showed a different enzyme activity for the antioxidant protein in the various tissues examined. In response to the 2,2'-azobiz(2-amidinopropane) dihydrochloride (AAPH) injection, the Tg rats showed a lower level of antioxidant and H2O2 concentration as the activity of the antioxidant enzyme was maintained at a higher level in the Tg rats than in the non-Tg rats. Also, the neutrophil-to-lymphocyte ratio was significantly increased in this Tg rat, even though the level of corticosterone remained unchanged in both genotypes. Thus, the results of this study demonstrated that the CMV/GFP-hSelM Tg rat can serve as an animal model for the maintenance of a high level of antioxidant status and can be used to study the biological function of selenoprotein in infectious diseases, cardiovascular disease and cancer.
authors.affiliation: Laboratory Animal Resources Team, National Institute of Toxicological Research, Korean FDA, Seoul 122-704, Korea. dyhwang@kfda.go.kr
authors.forename: Dae Youn
authors.initials: DY
authors.lastname: Hwang
authors.forename: Ji Soon
authors.initials: JS
authors.lastname: Sin
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Su Youn
authors.initials: SY
authors.lastname: Yim
authors.forename: Yong Kyu
authors.initials: YK
authors.lastname: Kim
authors.forename: Chuel Kyu
authors.initials: CK
authors.lastname: Kim
authors.forename: Byoung Guk
authors.initials: BG
authors.lastname: Kim
authors.forename: Sun Bo
authors.initials: SB
authors.lastname: Shim
authors.forename: Seung Wan
authors.initials: SW
authors.lastname: Jee
authors.forename: Su Hae
authors.initials: SH
authors.lastname: Lee
authors.forename: Chang Joon
authors.initials: CJ
authors.lastname: Bae
authors.forename: Byoung Chun
authors.initials: BC
authors.lastname: Lee
authors.forename: Mee Kyung
authors.initials: MK
authors.lastname: Jang
authors.forename: Jung Sik
authors.initials: JS
authors.lastname: Cho
authors.forename: Kab Ryong
authors.initials: KR
authors.lastname: Chae
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000378:metabolism*; D003345:Corticosterone / Q000378:metabolism; D003587:Cytomegalovirus; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D005979:Glutathione Peroxidase / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D051140:Selenoproteins / Q000235:genetics* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D000975:Antioxidants; C448999:SELM protein, human; D051140:Selenoproteins; D049452:Green Fluorescent Proteins; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003345:Corticosterone