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Enhanced cadmium-induced testicular necrosis and renal proximal tubular damage caused by gene-dose increase in a Slc39a8-transgenic mouse line

WANG, BIN
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172086886

Abstract Details

2007, MS, University of Cincinnati, Medicine : Toxicology (Environmental Health).
Resistance to cadmium (Cd)-induced testicular necrosis is an autosomal recessive trait defined as the Cdmlocus. Using positional cloning, we previously identified the Slc39a8(encoding an apical-surface ZIP8 transporter) as the gene most likely responsible for the phenotype. In situ hybridization revealed that endothelial cells of the testis vasculature express high ZIP8 levels in two sensitive inbred mouse strains and negligible amounts in two resistant strains. In the present study, we isolated a 170.6-kb bacterial artificial chromosome (BAC), carrying only the Slc39a8gene, from a Cd-sensitive 129/SvJ BAC library and generated BAC-transgenic mice. The BTZIP8-3 line, having three copies of the 129/SvJ Slc39a8gene inserted into the Cd-resistant C57BL/6J genome, showed tissue-specific ZIP8 mRNA expression similar to wild-type mice––mainly in lung, testis and kidney; the ~2.5-fold greater expression paralleled the fact that the BTZIP8-3 line has five copies, whereas wild-type mice have two copies, of the Slc39a8gene. The ZIP8 mRNA and protein localized especially to endothelial cells of the testis vasculature in BTZIP8-3 mice. Cd treatment reversed Cd-resistance (seen in non-transgenic littermates) to Cd-sensitivity in BTZIP8-3 mice; reversal of the testicular necrosis phenotype confirms that Slc39a8is unequivocally the Cdm locus. ZIP8 mRNA and protein also localized specifically to the apical surface of proximal tubule cells in the BTZIP8-3 kidney. Cd treatment caused acute renal failure and signs of proximal tubular damage in the BTZIP8-3 but not non-transgenic littermates. BTZIP8-3 mice should be a useful model for studying Cd-induced disease in kidney.
Dr. Daniel Nebert (Advisor)
45 p.
Health Sciences, Toxicology

Recommended Citations

Citations

  • WANG, B. (2007). Enhanced cadmium-induced testicular necrosis and renal proximal tubular damage caused by gene-dose increase in a Slc39a8-transgenic mouse line [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172086886

    APA Style (7th edition)

  • WANG, BIN. Enhanced cadmium-induced testicular necrosis and renal proximal tubular damage caused by gene-dose increase in a Slc39a8-transgenic mouse line. 2007. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172086886.

    MLA Style (8th edition)

  • WANG, BIN. "Enhanced cadmium-induced testicular necrosis and renal proximal tubular damage caused by gene-dose increase in a Slc39a8-transgenic mouse line." Master's thesis, University of Cincinnati, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172086886

    Chicago Manual of Style (17th edition)

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© 2006, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.