Testicular teratocarcinomas are almost unknown in mice except in the inbred strain 129/Sv and congenic and recombinant strains we have derived from it. One-third of the males of one of our congenic strains, 129/Sv-ter, have spontaneous congenital teratomas. This high incidence is due to a mutation, designated """"""""teratoma"""""""" (ter), that occurred in one of our colonies many years ago. Teratomas are derived from primordial germ cells that begin to develop parthenogenetically within the seminiferous tubules. Ninety-five percent of ter/ter males have teratomas and most of them are bilateral. Seventeen percent of ter/+, and only 1% of +/+ males have teratomas. Strain 129/Sv-ter was derived from strain 129/Sv and they are genetically alike except for the ter allele. We will introduce ter onto the backgrounds of several strains that are highly susceptible to experimentally induced teratocarcinogenesis but have very low incidences or lack spontaneous teratomas. Testicular teratomas can be experimentally induced in some strains of mice by grafting testicular primordia from 12-day male fetuses to the testes of adults. The grafts develop into testes with teratomas. Strains 129 and A/He are more susceptible to experimental teratocarcinogenesis than other strains. We have made recombinant inbred (RI) strains using them as progenitors. Some of them are even more susceptible to experimental teratocarcinogenesis than either parent strain. Strangely, only 2% of the males of these RI strains have spontaneous teratomas. We will introduce the ter allele onto the genetic background of these strains and expect that this will increase the incidence of spontaneous teratomas. We will also map the ter locus and determine whether ter is an allele of W. In order to understand the mechanism of teratocarcinogenesis at the cellular and molecular levels, we will ask the question how the germ cells of 129/Sv, 129/Sv-ter and A/He strains are different from those of C3H and other non-susceptible strains. We plan to establish an in vitro culture system of primordial germ (PG) cells. These PG cells will be analyzed karyologically, and injected into adult testes to see if they form teratocarcinomas. To identify ter-specific gene(s), we will construct cDNA clone banks from the PG cells, and the different clones between the two strains will be isolated by the subtraction hybridization method.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Reproductive Endocrinology Study Section (REN)
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Jackson Laboratory
Bar Harbor
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Walt, H; Oosterhuis, J W; Stevens, L C (1993) Experimental testicular germ cell tumorigenesis in mouse strains with and without spontaneous tumours differs from development of germ cell tumours of the adult human testis. Int J Androl 16:267-71
Taketo, M; Schroeder, A C; Mobraaten, L E et al. (1991) FVB/N: an inbred mouse strain preferable for transgenic analyses. Proc Natl Acad Sci U S A 88:2065-9
Muntener, M; Kagi, U; Stevens, L C et al. (1990) Innervation and maturation of muscular tissue in testicular teratomas in strain 129/Sv-ter mice. Virchows Arch B Cell Pathol Incl Mol Pathol 59:223-9