Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs.

The Journal of Biological Chemistry
Xiangbing MengKimberly K Leslie

Abstract

Increased expression of metadherin (MTDH, also known as AEG-1 and 3D3/LYRIC) has been associated with drug resistance, metastasis, and angiogenesis in a variety of cancers. However, the specific mechanisms through which MTDH is involved in these processes remain unclear. To uncover these mechanisms, we generated Mtdh knock-out mice via a targeted disruption of exon 3. Homozygous Mtdh knock-out mice are viable, but males are infertile. The homozygous male mice present with massive loss of spermatozoa as a consequence of meiotic failure. Accumulation of γ-H2AX in spermatocytes of homozygous Mtdh knock-out mice confirms an increase in unrepaired DNA breaks. We also examined expression of the DNA repair protein Rad18, which is regulated by MTDH at the post-transcriptional level. In testes from Mtdh exon 3-deficient mice, Rad18 foci were increased in the lumina of the seminiferous tubules. The Piwi-interacting RNA (piRNA)-interacting protein Mili was expressed at high levels in testes from Mtdh knock-out mice. Accordingly, genome-wide small RNA deep sequencing demonstrated altered expression of piRNAs in the testes of Mtdh knock-out mice as compared with wild type mice. In addition, we observed significantly reduced expression of mi...Continue Reading

References

Oct 2, 2001·Mechanisms of Development·S Kuramochi-MiyagawaT Nakano
Apr 12, 2003·Developmental Cell·Oscar Fernandez-CapetilloAndré Nussenzweig
Jan 23, 2004·Development·Satomi Kuramochi-MiyagawaToru Nakano
Aug 17, 2004·Trends in Cell Biology·Katrin Gudmundsdottir, Alan Ashworth
Nov 14, 2006·Biochemical and Biophysical Research Communications·Keiyo TakuboToshio Suda
Jun 2, 2007·The EMBO Journal·Tina ThorslundStephen C West
Mar 5, 2008·Cancer Research·Devanand SarkarPaul B Fisher
Apr 29, 2008·Biochemical and Biophysical Research Communications·S C AshD E Britt
Dec 11, 2008·Mechanisms of Development·Jinghua SunSatoshi Tateishi
Apr 7, 2009·Current Biology : CB·Jianquan WangHaifan Lin
Sep 3, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guohong HuYibin Kang
Apr 15, 2010·Cancer Research·Byoung Kwon YooDevanand Sarkar
Aug 26, 2010·Gene Expression Patterns : GEP·Hyun Yong JeonPaul B Fisher
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Byoung Kwon YooDevanand Sarkar
Dec 27, 2011·The Journal of Biological Chemistry·Xiangbing MengKimberly K Leslie
Jun 13, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jyoti SrivastavaDevanand Sarkar
Oct 5, 2012·Reproduction : the Official Journal of the Society for the Study of Fertility·Josefa Blanco-Rodríguez
Nov 21, 2012·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Shinichiro Chuma, Toru Nakano
Jul 31, 2013·Advances in Cancer Research·Devanand Sarkar, Paul B Fisher
Jul 31, 2013·Advances in Cancer Research·Xiangbing MengKimberly K Leslie
Jul 31, 2013·Advances in Cancer Research·Devanand Sarkar
Jul 31, 2013·Advances in Cancer Research·Devanand Sarkar, Paul B Fisher
Jun 22, 2014·ELife·Johanna Liinamaria SyrjänenOwen Richard Davies
Aug 16, 2014·Cancer Research·Jyoti SrivastavaDevanand Sarkar
Sep 7, 2014·Cancer Research·Chadia L RobertsonDevanand Sarkar

❮ Previous
Next ❯

Citations

Mar 5, 2016·Journal of Assisted Reproduction and Genetics·Sezgin GunesRamazan Asci
Apr 23, 2016·Biochimica Et Biophysica Acta·ShaoPeng WangQuan Zou
Apr 19, 2018·Journal of Cellular Physiology·Zahra PourmoghadamMehdi Yousefi
Jun 14, 2015·The Journal of Biological Chemistry·Chadia L RobertsonDevanand Sarkar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.