Skip Navigation



Human Molecular Genetics Advance Access published online on January 23, 2009
Human Molecular Genetics, doi:10.1093/hmg/ddp045
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
18/8/1395    most recent
ddp045v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Heaney, J. D.
Right arrow Articles by Nadeau, J. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Heaney, J. D.
Right arrow Articles by Nadeau, J. H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Deletion of eIF2beta suppresses testicular cancer incidence and causes recessive lethality in agouti-yellow mice

Jason D. Heaney*, Megan V. Michelson, Kirsten K. Youngren, Man-Yee J. Lam and Joseph H. Nadeau

Department of Genetics and Case Comprehensive Cancer Center Case Western Reserve University School of Medicine 10900 Euclid Ave Cleveland OH 44120 USA

* To whom correspondence should be addressed: Jason D. Heaney, Ph.D. Department of Genetics Case Western Reserve University 10900 Euclid Ave Cleveland OH 44120 Tel: 1 (216) 368-0626 Fax: 1 (216) 368-3432 E-mail: jason.heaney{at}case.edu

Received December 30, 2008; Revised January 20, 2009; Accepted January 21, 2009

The agouti-yellow (Ay) deletion is the only genetic modifier known to suppress testicular germ cell tumor (TGCT) susceptibility in mice or humans. The Ay mutation deletes Raly and Eif2s2, and induces the ectopic expression of agouti, all of which are potential TGCT-modifying mutations. Here we report that the reduced TGCT incidence of heterozygous Ay mice and the recessive embryonic lethality of Ay are caused by the deletion of Eif2s2, the beta subunit of translation initiation factor eIF2. We found that the incidence of affected males was reduced 2-fold in mice that were partially deficient for Eif2s2 and that embryonic lethality occurred near the time of implantation in mice that were fully deficient for Eif2s2. By contrast, neither reduced expression of Raly in gene-trap mice nor ectopic expression of agouti in transgenic or viable-yellow (Avy) mutants affected TGCT incidence or embryonic viability. In addition, we provide evidence that partial deficiency of Eif2s2 attenuated germ cell proliferation and differentiation, both of which are important to TGCT formation. These results show that germ cell development and TGCT pathogenesis are sensitive to the availability of the eIF2 translation initiation complex and to changes in the rate of translation.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Hum Mol GenetHome page
J. H. Nadeau
Transgenerational genetic effects on phenotypic variation and disease risk
Hum. Mol. Genet., October 15, 2009; 18(R2): R202 - R210.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.