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.
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.
Hwang
Dae Youn
DY
Laboratory Animal Resources Team, National Institute of Toxicological Research, Korean FDA, Seoul 122-704, Korea. dyhwang@kfda.go.kr
Sin
Ji Soon
JS
Kim
Min Sun
MS
Yim
Su Youn
SY
Kim
Yong Kyu
YK
Kim
Chuel Kyu
CK
Kim
Byoung Guk
BG
Shim
Sun Bo
SB
Jee
Seung Wan
SW
Lee
Su Hae
SH
Bae
Chang Joon
CJ
Lee
Byoung Chun
BC
Jang
Mee Kyung
MK
Cho
Jung Sik
JS
Chae
Kab Ryong
KR
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*
D000975:Antioxidants; C448999:SELM protein, human; D051140:Selenoproteins; D049452:Green Fluorescent Proteins; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003345:Corticosterone