Chromosome X modulates incidence of testicular germ cell tumors in Ter mice (original) (raw)

Abstract

Germ cell tumor development in humans has been proposed to be part of testicular dysgenesis syndrome (TDS), which manifests as undescended testes, sterility, hypospadias, and, in extreme cases, as germ cell tumors. Males of the Ter mouse strain show interesting parallels to TDS because they either lack germ cells and are sterile or develop testicular germ cell tumors. We found that these defects in Ter mice are due to mutational inactivation of the Dead-end (Dnd1) gene. Here we report that chromosome X modulates germ cell tumor development in Ter mice. We tested whether the X or the Y chromosome influences tumor incidence. We used chromosome substitution strains to generate two new mouse strains: 129-Ter/Ter that carry either a C57BL/6J (B6)-derived chromosome (Chr) X or Y. We found that Ter/Ter males with B6-Chr X, but not B6-Chr Y, showed a significant shift in propensity from testicular tumor development to sterile testes phenotype. Thus, our studies provide unambiguous evidence that genetic factors from Chr X modulate the incidence of germ cell tumors in mice with inactivated Dnd1.

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Acknowledgments

The authors thank Lianchun Xiao for help with statistical calculations and Glenda Seawood for assistance with mouse husbandry. They also thank J. H. Nadeau for critical reading of the manuscript. This work was supported by National Cancer Institute grants CA93754 and CA75056 and David Carmine Cancer Research Fund.

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Authors and Affiliations

1. Department of Cancer Genetics, University of Texas, MD Anderson Cancer Center, Houston, Texas, 77005, USA
   Shirley Hammond, Rui Zhu & Angabin Matin
2. Department of Genetics, Case Western Reserve University, Cleveland, Ohio, 44106, USA
   Kirsten K. Youngren, Josephine Lam & Philip Anderson

Authors

1. Shirley Hammond
2. Rui Zhu
3. Kirsten K. Youngren
4. Josephine Lam
5. Philip Anderson
6. Angabin Matin

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Correspondence toAngabin Matin.

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Hammond, S., Zhu, R., Youngren, K.K. et al. Chromosome X modulates incidence of testicular germ cell tumors in Ter mice.Mamm Genome 18, 832–838 (2007). https://doi.org/10.1007/s00335-007-9075-8

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• Received: 14 August 2007
• Accepted: 16 October 2007
• Published: 30 November 2007
• Issue Date: December 2007
• DOI: https://doi.org/10.1007/s00335-007-9075-8

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