McInnis Christine M, Bonthuis Paul J, Rissman Emilie F, Park Jin Ho
Psychology Department, University of Massachusetts, Boston, Boston, MA 02125, United States.
Department of Biochemistry & Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, United States.
Horm Behav. 2016 Apr;80:132-138. doi: 10.1016/j.yhbeh.2016.02.003. Epub 2016 Mar 2.
The importance of gonadal steroids in modulating male sexual behavior is well established. Individual differences in male sexual behavior, independent of gonadal steroids, are prevalent across a wide range of species, including man. However, the genetic mechanisms underlying steroid-independent male sexual behavior are poorly understood. A high proportion of B6D2F1 hybrid male mice demonstrates steroid-independent male sexual behavior (identified as "maters"), providing a mouse model that opens up avenues of investigation into the mechanisms regulating male sexual behavior in the absence of gonadal hormones. Recent studies have revealed several proteins that play a significant factor in regulating steroid-independent male sexual behavior in B6D2F1 male mice, including amyloid precursor protein (APP), tau, and synaptophysin. The specific goals of our study were to determine whether steroid-independent male sexual behavior was a heritable trait by determining if it was dependent upon the behavioral phenotype of the B6D2F1 sire, and whether the differential expression of APP, tau, and synaptophysin in the medial preoptic area found in the B6D2F1 sires that did and did not mate after gonadectomy was similar to those found in their male offspring. After adult B6D2F1 male mice were bred with C57BL/6J female mice, they and their male offspring (BXB1) were orchidectomized and identified as either maters or "non-maters". A significant proportion of the BXB1 maters was sired only from B6D2F1 maters, indicating that the steroid-independent male sexual behavior behavioral phenotype of the B6D2F1 hybrid males, when crossed with C57BL/6J female mice, is inherited by their male offspring. Additionally, APP, tau, and synaptophysin were elevated in in the medial preoptic area in both the B6D2F1 and BXB1 maters relative to the B6D2F1 and BXB1 non-maters, respectively, suggesting a potential genetic mechanism for the inheritance of steroid-independent male sexual behavior.
性腺类固醇在调节雄性性行为中的重要性已得到充分证实。在包括人类在内的广泛物种中，雄性性行为的个体差异独立于性腺类固醇，这种差异普遍存在。然而，与性腺类固醇无关的雄性性行为背后的遗传机制却知之甚少。高比例的B6D2F1杂交雄性小鼠表现出与性腺类固醇无关的雄性性行为（被认定为“交配者”），这提供了一个小鼠模型，为研究在没有性腺激素的情况下调节雄性性行为的机制开辟了途径。最近的研究揭示了几种在调节B6D2F1雄性小鼠与性腺类固醇无关的雄性性行为中起重要作用的蛋白质，包括淀粉样前体蛋白（APP）、tau蛋白和突触素。我们研究的具体目标是，通过确定与性腺类固醇无关的雄性性行为是否依赖于B6D2F1父本的行为表型，来判断其是否为一种可遗传的性状；以及在性腺切除术后交配和未交配的B6D2F1父本中，内侧视前区APP、tau蛋白和突触素的差异表达是否与其雄性后代中的情况相似。成年B6D2F1雄性小鼠与C57BL/6J雌性小鼠交配后，它们及其雄性后代（BXB1）接受去势手术，并被认定为交配者或“非交配者”。相当比例的BXB1交配者仅由B6D2F1交配者所生，这表明当B6D2F1杂交雄性小鼠与C57BL/6J雌性小鼠杂交时，其与性腺类固醇无关的雄性性行为表型会被其雄性后代继承。此外，相对于B6D2F1和BXB1非交配者，APP、tau蛋白和突触素在B6D2F1和BXB1交配者的内侧视前区中均有所升高，这表明了与性腺类固醇无关的雄性性行为遗传的潜在遗传机制。
