International Mammalian Genome Society


The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

E28 Mapping Germ Cell Tumor Susceptibility Genes Using a Consomic Strain and Derived Congenic Strains

Kirsten Youngren, Angabin Matin and Joseph Nadeau. Dept. of Genetics, Case Western Reserve University, Cleveland, OH

Although testicular germ cell tumors (TGCTs) are the most common cancers in young males, their genetic control in humans is poorly understood. The 129/Sv strain of mice serves as a model system for TGCTs. This strain develops TGCT at a frequency of 1-10% depending on the subline. Genetic mutations such as Ter, MgfSl-J and Trp53 on the 129 background further increase TGCT frequency. Using a 129.MOLF-Chr 19 consomic strain (or Chromosome Substitution Strain), we have identified a novel susceptibility locus derived from the MOLF/Ei strain, Tgct1, which predisposes to a very high TGCT frequency when present on the 129/Sv background. Eighty-two percent of males homosomic for MOLF Chr 19 have TGCT whereas 24% of heterosomic mice develop TGCT. Approximately 57% of the tumors from homosomic mice were bilateral whereas all tumors from heterosomic mice were unilateral. The susceptibility locus for bilateral tumors, Tgct1, was mapped near D19Mit5 on the central portion of Chr 19. However, although a large number of males from the consomic strain had unilateral TGCTs (43%), we were unable to identify a specific locus on Chr 19 that predisposed to unilateral tumors. This suggests that more than one locus or interaction of 129/Sv and MOLF loci on Chr 19 may predispose to unilateral tumors. To dissect this phenomenon, we are deriving congenic strains from the 129.MOLF-Chr 19 consomic strain. Congenics carrying the proximal third, middle and distal third of the MOLF/Ei Chr 19 on a 129/Sv background are being made. The tumor frequency and tumor type (unilateral vs. bilateral) of these congenics will be examined and compared. These congenics will help define the location of Tgct1 more precisely for subsequent gene identification and also determine whether other regions on Chr 19 are responsible for unilateral TGCT development.

 


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