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Tissue Distribution and Mitochondrial Localization of Human Thioredoxin 2 (hTrx2) in transgenic mice
Author(s) -
He Min,
Cai Jiyang,
Go YoungMi,
Halvey Patrick,
Hansen Jason,
Jones Dean P
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb102-a
Subject(s) - biology , transgene , microbiology and biotechnology , genetically modified mouse , mitochondrion , thioredoxin , gene knockdown , apoptosis , gene , biochemistry
Trx2 is a critical regulator of cell survival and mitochondria‐mediated apoptosis. In vitro studies show overexpression of Trx2 confers an increase in mitochondria membrane potential and resistance to apoptosis induced by peroxides and etoposide. Knockdown of Trx2 expression results in apoptosis. Knockout Trx2 mice died in early embryonic development. To gain further insight into the roles of Trx2 in vivo, we established hTrx2 transgenic mouse model with hTrx2 expression under a CAG promoter. A C‐terminal V5 epitope tag was included to aid the detection of the transgene product. In all 3 founder lines that were generated, high expression of hTrx2 was observed in heart, pancreas, and skeletal muscle, while the expression in brain, lung and kidney were lower. This tissue distribution quantitatively differed from that of endogenous mouse Trx2 and cytochrome c. Western blot analyses of extracts from isolated mitochondria of liver, heart and skeletal muscle showed that hTrx2 was expressed in mitochondria in a processed form with removal of MLS. Thus, the hTrx2 was expressed in the mice as the mature form localized in mitochondria. Quantification of mRNA level by real‐time PCR showed that mRNA distribution did not correlate with the protein expression. These results indicate that mechanism other than transcription control hTrx2 expression. The results indicate that this transgenic mouse model will provide a useful way to observe the function of Trx2 in normal and pathological processes.