Spontaneous malignant granulosa cell tumors in ovaries of young SWR mice

Abstract

Granulosa cell tumors (GCT) of the ovary appear spontaneously at 4-6 weeks of age in SWR/J and in SWR/Bm inbred strain mice, with a maximum incidence reached by 10 weeks. Cancer was confirmed by metastasis to abdominal organs and by transplantability of primary tumors to histocompatible hosts. Results of genetic crosses showed that GCT appear in SWR X SJL F1 but not in SJL X SWR F1 nor in other F1 females derived from matings of SWR mice with A/HeJ, C57BL/6By, CBA/J, or DBA/2J mice. These findings suggest the maternal transmission of GCT susceptibility. Recombinant inbred strains SWXJ were produced from a progenitor mating of a SWR female to a SJL male. At F20, females in 3 of 14 SWXJ strains developed GCT, with one strain displaying a 5-fold increase in incidence. Embryo transfer studies with SWXJ-6 and -9 mice suggested that maternal transmission was most likely via the fertilized egg rather than through milk or placenta-uterine contact. Analysis of metaphase chromosomes indicated that the modal number in tumors and bone marrow was 40 (2n = 40) with 2 X chromosomes present. Gross chromosomal aberrations were not detected. A working hypothesis proposes that interaction of a unique SWR factor, perhaps cytoplasmic, with nuclear genomic material common to Swiss mouse stocks results in occurrence of GCT in young SWR and SWR-derived mice.