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Sexual behavior was observed in male mice that were homozygous for a null mutation of the c-fos proto-oncogene, as well as in heterozygous mutants and wild-type controls. The onset of mounting was slower and the subsequent mounting rate was significantly lower in homozygous mutants than in either group of controls. Even so, a similar percentage of males of each genotype achieved ejaculation, and ejaculation latencies were equivalent in these mice. Likewise, in males that intromitted, the intromission efficiency and the number of intravaginal thrusts/intromission were similar among the three genotypes. The nuclear protein product (Fos) of c-fos was visualized immunocytochemically in the brains of heterozygous male mice 1 h after they exhibited a series of mounts, with or without intromission, leading to an ejaculation. As in the male of several other rodent species, nuclear Fos immunoreactivity was augmented in neurons of limbic and midbrain regions thought to convey olfactory/vomeronasal and genital/somatosensory information, respectively, to the medial preoptic area following contact with an estrous female. One interpretation of our behavioral results is that in the absence of normal neuronal c-fos expression, sensory stimuli that impinge on the male brain during mating lose their ability to initiate a cascade of further gene transcription events that otherwise control the rate at which a male reorients towards and mounts an estrous female during an ejaculatory series. Alternatively, the c-fos null mutation may disrupt normal neural development, leading to a structural change that mediates the observed deficit in mounting capacity.

Effect of a Null Mutation of the c-fos Proto-Oncogene on Sexual Behavior of Male Mice1