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. 2000 Dec 19;97(26):14737-41.
doi: 10.1073/pnas.250473597.

Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO)

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Abolition of male sexual behaviors in mice lacking estrogen receptors alpha and beta (alpha beta ERKO)

S Ogawa et al. Proc Natl Acad Sci U S A. .

Abstract

Male mice with a knockout of the estrogen receptor (ER)-alpha gene, a ligand-activated transcription factor, showed reduced levels of intromissions and no ejaculations whereas simple mounting behavior was not affected. In contrast, all components of sexual behaviors were intact in male mice lacking the novel ER-beta gene. Here we measure the extent of phenotype in mice that lack both ER-alpha and ER-beta genes (alphabetaERKO). alphabetaERKO male mice did not show any components of sexual behaviors, including simple mounting behavior. Nor did they show ultrasonic vocalizations during behavioral tests with receptive female mice. On the other hand, reduced aggressive behaviors of alphabetaERKO mice mimicked those of single knockout mice of ER-alpha gene (alphaERKO). They showed reduced levels of lunge and bite aggression, but rarely showed offensive attacks. Thus, either one of the ERs is sufficient for the expression of simple mounting in male mice, indicating a redundancy in function. Offensive attacks, on the other hand, depend specifically on the ER-alpha gene. Different patterns of natural behaviors require different patterns of functions by ER genes.

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Figures

Figure 1
Figure 1
Photomicrographs showing the AR-immunoreactive (IR) cells (stained with rabbit polyclonal antibody, Affinity Bioreagent) in the medial preoptic area, where gonadal steroids regulate male sexual behaviors. AR-IR cells were not at all reduced and may have been increased in αβERKO mice (B) compared with αβWT mice (A) brains. (Scale bar: 100 μm.)
Figure 2
Figure 2
Effects of ERα and/or ERβ gene disruption on (A) latency to the first aggressive act, (B) cumulative duration of all aggressive bouts, (C) number of lunge and bite aggression bouts, (D) number of offensive attack bouts, and (E) cumulative duration of attempted sexual behaviors toward male intruder mice, during resident-intruder tests. There were significant genotype differences in total aggression duration (B) and number of offensive attack bouts (D) throughout the four tests (P < 0.01) but not in the number of lunge and bite aggression bouts (C). Post hoc comparisons for the main effects of genotype revealed that both αβERKO and αERKO mice were significantly less aggressive compared with αβWT as well as βERKO. On the other hand, there was a significant (P < 0.01) interaction between genotype and test in aggression latency (A). Latencies in αβWT and βERKO males steadily decreased with the repetition of the tests, whereas those of αβERKO were shorter in the first and third tests compared with the second and fourth tests. Post hoc comparisons for genotype differences, therefore, were performed in each test separately for this measurement. Finally, αβWT showed substantial amounts of sexual behaviors in the first test compared with other three genotypes of mice, although overall genotype differences were not significant. a: P < 0.05 vs αβWT, b: P < 0.05 vs βERKO.

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