PMID- 12588969
OWN - NLM
STAT- MEDLINE
DCOM- 20030404
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 23
IP  - 5
DP  - 2003 Mar
TI  - Selective removal of the selenocysteine tRNA [Ser]Sec gene (Trsp) in mouse 
      mammary epithelium.
PG  - 1477-88
AB  - Mice homozygous for an allele encoding the selenocysteine (Sec) tRNA [Ser]Sec 
      gene (Trsp) flanked by loxP sites were generated. Cre recombinase-dependent 
      removal of Trsp in these mice was lethal to embryos. To investigate the role of 
      Trsp in mouse mammary epithelium, we deleted this gene by using transgenic mice 
      carrying the Cre recombinase gene under control of the mouse mammary tumor virus 
      (MMTV) long terminal repeat or the whey acidic protein promoter. While both 
      promoters target Cre gene expression to mammary epithelium, MMTV-Cre is also 
      expressed in spleen and skin. Sec tRNA [Ser]Sec amounts were reduced by more than 
      70% in mammary tissue with either transgene, while in skin and spleen, levels 
      were reduced only with MMTV-Cre. The selenoprotein population was selectively 
      affected with MMTV-Cre in breast and skin but not in the control tissue, kidney. 
      Moreover, within affected tissues, expression of specific selenoproteins was 
      regulated differently and often in a contrasting manner, with levels of Sep15 and 
      the glutathione peroxidases GPx1 and GPx4 being substantially reduced. Expression 
      of the tumor suppressor genes BRCA1 and p53 was also altered in a contrasting 
      manner in MMTV-Cre mice, suggesting greater susceptibility to cancer and/or 
      increased cell apoptosis. Thus, the conditional Trsp knockout mouse allows 
      tissue-specific manipulation of Sec tRNA and selenoprotein expression, suggesting 
      that this approach will provide a useful tool for studying the role of 
      selenoproteins in health.
FAU - Kumaraswamy, Easwari
AU  - Kumaraswamy E
AD  - Section on Molecular Biology of Selenium, Basic Research Laboratory, Center for 
      Cancer Research, National Cancer Institute, National Institutes of Health, 
      Bethesda, Maryland 20892, USA.
FAU - Carlson, Bradley A
AU  - Carlson BA
FAU - Morgan, Fanta
AU  - Morgan F
FAU - Miyoshi, Keiko
AU  - Miyoshi K
FAU - Robinson, Gertraud W
AU  - Robinson GW
FAU - Su, Dan
AU  - Su D
FAU - Wang, Shulin
AU  - Wang S
FAU - Southon, Eileen
AU  - Southon E
FAU - Tessarollo, Lino
AU  - Tessarollo L
FAU - Lee, Byeong Jae
AU  - Lee BJ
FAU - Gladyshev, Vadim N
AU  - Gladyshev VN
FAU - Hennighausen, Lothar
AU  - Hennighausen L
FAU - Hatfield, Dolph L
AU  - Hatfield DL
LA  - eng
GR  - CA080946/CA/NCI NIH HHS/United States
GR  - R37 GM065204/GM/NIGMS NIH HHS/United States
GR  - R01 CA080946/CA/NCI NIH HHS/United States
GR  - GM065204/GM/NIGMS NIH HHS/United States
GR  - R01 GM065204/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Proteins)
RN  - 0 (RNA, Transfer, Amino Acyl)
RN  - 0 (Selenoproteins)
RN  - 0 (selenocysteinyl-tRNA)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
SB  - IM
MH  - Alleles
MH  - Animals
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Breast/*metabolism
MH  - Chromatography
MH  - Crosses, Genetic
MH  - Epithelium/*metabolism
MH  - Gene Deletion
MH  - Genes, BRCA1
MH  - Genes, p53/genetics
MH  - Genetic Vectors
MH  - Glutathione Peroxidase/metabolism
MH  - Heterozygote
MH  - Kidney/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Models, Genetic
MH  - Phenotype
MH  - Promoter Regions, Genetic
MH  - Proteins/metabolism
MH  - RNA, Transfer, Amino Acyl/*genetics/*metabolism
MH  - Recombination, Genetic
MH  - Selenoproteins
MH  - Tissue Distribution
MH  - Transgenes
PMC - PMC151713
EDAT- 2003/02/18 04:00
MHDA- 2003/04/05 05:00
PMCR- 2003/03/01
CRDT- 2003/02/18 04:00
PHST- 2003/02/18 04:00 [pubmed]
PHST- 2003/04/05 05:00 [medline]
PHST- 2003/02/18 04:00 [entrez]
PHST- 2003/03/01 00:00 [pmc-release]
AID - 1446 [pii]
AID - 10.1128/MCB.23.5.1477-1488.2003 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2003 Mar;23(5):1477-88. doi: 10.1128/MCB.23.5.1477-1488.2003.