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Hermaphroditism, Sex Chromosomal Mosaicism and Germ Cell Selection in Allophenic Mice¹

The Institute for Cancer Research, Philadelphia, Pennsylvania

Abstract

Allophenic mice, experimentally obtained by aggregating pairs of early embryos to form a composite individual, offer new possibilities for exploration of basic questions in reproductive biology. The precocious and persistent association of different allelic genotypes, or sex chromosome karyotypes, could disclose controls governing germinal and somatic sex differentiation and function.

The simultaneous presence of XX ("female") and XY ("male") cells might be expected in 50% of the cases. In a preliminary classification of 463 allophenic mice, however, only six (1.3%) hermaphrodites were found. The remainder of the allophenics were divided phenotypically into approximately equal numbers of males and females. The incidence of sterility in test-mated males and females was also surprisingly low (18 sterile: 288 fertile). The paucity of intersexes does not appear to result from gross selection against animals of intersexual phenotype. It may in part arise from competition and selection between XX and XY cells during early reproductive development. Of the "missing" or inapparent XX/XY mosaics, some have been identified by means of karyotype analyses among the sterile males and females and among the fertile male population as well. (Fertile females have not yet been examined.) The normalcy of sex ratios among the many progeny (29,384) of allophenic mice explicitly rules out any functional sex reversal of germ cells in the allophenics. Mammals in general may, therefore, be unique among vertebrates in having achieved a relatively stable genetic mechanism for sex determination.

Thirty germinal mosaics were obtained, each having two genotypes of functional germ cells with respect to various loci, such as coat color markers. The males provide the first evidence that selection favoring one of two germ cell types can occur during diploid phases of mammalian gametogenesis, perhaps beginning even before birth. The facts suggest that "hidden" selection against mutant germ cells might complicate mutational studies, and could lead to underestimation of mutation rates.

The allophenic germinal mosaics also establish that the minimum primordial germ cell number is two; from our previous studies, it is known that the maximum is nine. Since all germ cells in the adult mouse arise as only two to nine clones, early errors or defects in the few initial cells can have enormously magnified consequences for reproduction.

¹ These investigations were supported by U. S. Public Health Service Research Grants No. HD 01646 (formerly CA 05201) and CA 06927.