International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)


POSTER 21 - GENETIC CONTROL OF SUSCEPTIBILITY TO SPONTANEOUS TESTICULAR GERM CELL TUMORS IN THE 129.MOLF-CHR19 CHROMOSOME SUBSTITUTION STRAIN AND DERIVED CONGENIC STRAINS

K Youngren
Case Western Reserve University

2) Handel MA, 3) Matin A, 1) Nadeau JH
1) CWRU,  2) University of Tennessee, 3) University of Texas

Testicular germ cell tumors (TGCTs) are the most common solid cancers affecting young men. Although there is evidence for genetic predisposition to TGCTs, the genetic control of susceptibility is poorly understood. The 129S1/SvImJ mouse strain is an excellent model system for studying TGCTs. This strain develops TGCTs at a frequency of 1-10% depending on the subline. We previously reported a new mouse strain, the 129.MOLF-Chr19 Chromosome Substitution Strain (CSS), which develops spontaneous TGCTs at a high frequency. This strain was made by replacing chromosome (Chr) 19 of the 129 strain with the homologous chromosome from the MOLF/Ei strain. 82% of males of the 129.MOLF-Chr19 strain develop TGCT and 57% of these TGCTs are bilateral. To characterize the genetic control of TGCT susceptibility in this CSS, we created a panel of congenic strains derived from the 129.MOLF-Chr19 strain. We found that multiple genes, alone and in combination, control susceptibility to TGCTs in a highly quantitative manner. We propose that these TGCTs result from disrupted testicular and spermatogenic developmental programs in hybrid genomes composed of distantly related mouse strains.  Given the evidence for the number and location of these genes, we are now using a novel speed mapping method with CSSs and congenic strains derived from them to rapidly localize the genes controlling TGCT susceptibility.


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