Selenoprotein expression is essential in endothelial cell development and cardiac muscle function.
LoxP-Cre technology was used to remove the selenocysteine tRNA gene, trsp, in either endothelial cells or myocytes of skeletal and heart muscle to elucidate the role of selenoproteins in cardiovascular disease. Loss of selenoprotein expression in endothelial cells was embryonic lethal. A 14.5-day-old embryo had numerous abnormalities including necrosis of the central nervous system, subcutaneous hemorrhage and erythrocyte immaturity. Loss of selenoprotein expression in myocytes manifested no apparent phenotype until about day 12 after birth. Affected mice had decreased mobility and an increased respiratory rate, which proceeded rapidly to death. Pathological analysis revealed that mice lacking trsp had moderate to severe myocarditis with inflammation extending into the mediastinitis. Thus, ablation of selenoprotein expression demonstrated an essential role of selenoproteins in endothelial cell development and in proper cardiac muscle function. The data suggest a direct connection between the loss of selenoprotein expression in these cell types and cardiovascular disease.
Shrimali
Rajeev K
RK
Molecular Biology of Selenium Section, Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Weaver
James A
JA
Miller
Georgina F
GF
Starost
Matthew F
MF
Carlson
Bradley A
BA
Novoselov
Sergey V
SV
Kumaraswamy
Easwari
E
Gladyshev
Vadim N
VN
Hatfield
Dolph L
DL
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D005838:Genotype; D006321:Heart / Q000254:growth & development* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D011247:Pregnancy; D012350:RNA, Transfer, Cys / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017279:Selenocysteine / Q000378:metabolism; D051140:Selenoproteins / Q000096:biosynthesis*; D012726:Sexual Behavior, Animal / Q000502:physiology
D012350:RNA, Transfer, Cys; D051140:Selenoproteins; D017279:Selenocysteine