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Genetic Regulation of Traits Essential for Spontaneous Ovarian Teratocarcinogenesis in Strain LT/Sv Mice: Aberrant Meiotic Cell Cycle, Oocyte Activation, and Parthenogenetic Development¹

The Jackson Laboratory, Bar Harbor, Maine 04609

Strain LT/Sv female mice show a high frequency of spontaneous ovarian teratomas arising from parthenogenetically activated follicular oocytes. LT/Sv oocytes also arrest at metaphase of meiosis I, rather than progressing through to metaphase II, as do almost all fully grown oocytes from most other strains. We investigated a new set of recombinant inbred strains derived from BALB/c and C58 (the progenitor strains of LT/Sv) and crosses of these two progenitor strains and found that metaphase I arrest is necessary, but not sufficient, to cause parthenogenetic activation. Occurrence of progeny with phenotypes more extreme than either parent (transgressive variation) suggests that these traits are polygenic and that LT/Sv mice inherited a novel combination of permissive alleles from their progenitor strains. Absence of teratomas from some LT-related strains demonstrate that metaphase I arrest and parthenogenetic activation are not sufficient for teratoma formation and that additional permissive alleles are required for teratocarcinogenesis. Finally, segregation analysis of teratoma formation in these strains suggests that a single autosomal gene derived from C57BL/6J mice is responsible for the high tumor incidence in one of these strains, LTXBO. Together these results show that metaphase I arrest, parthenogenetic activation of oocytes, and teratoma formation are multigenic traits involving a modest number of permissive alleles.

¹ This research was supported by National Cancer Institute Grants RO1-CA62392 (J. J. E. and K. W.) and ACS 279 (J. H. N. and D. S. V.) and by the National Cancer Institute of Canada with funds from the Terry Fox Run (J. H. N.).

² To whom requests for reprints should be addressed, at The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609. E-mail: jje@aretha.jax.org.

³ Present address: Department of Human Genetics, Montreal General Hospital, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4. Canada. E-mail: jnadeau@medcor.mcgill.ca.

Received 7/22/96. Accepted 9/16/96.

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