Germline Stem Cells

Volume 450 of the series Methods in Molecular Biology™ pp 211-231

Testicular Germ Cell Tumors in Mice

New Ways to Study a Genetically Complex Trait
  • Jason D. HeaneyAffiliated withDepartment of Genetics, Case Western Reserve University
  • , Joseph H. NadeauAffiliated withDepartment of Genetics, Case Western Reserve University

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Testicular germ cell tumors (TGCTs) are the most common cancer affecting young men. Although TGCTs are common and the genetic component of susceptibility is unusually strong, discovery of TGCT susceptibility genes in humans has been challenging. The 129/Sv inbred mouse strain is an important experimental model for studying the genetic control of TGCT susceptibility. It is the only inbred mouse strain with an appreciable frequency of spontaneous TGCTs. TGCTs in 129/Sv males share various developmental and histological characteristics with human pediatric TGCTs. As in humans, susceptibility in 129/Sv is a genetically complex trait that is too complex for conventional genetic approaches. However, several genetic variants, when congenic or isogenic on the 129/Sv background, act as genetic modifiers of TGCT susceptibility. Alternative experimental approaches based on these modifier genes can be used to unravel the complex genetic control of TGCT susceptibility. We discuss the application of modifier genes in genetic interaction tests and sensitized polygenic trait analyses toward the understanding of the complex genetics and biology of TGCT susceptibility in mice.


Consomic interaction Mouse Polygene QTL sensitized susceptibility testicular tumor modifier