Functional Analysis of Oxytocin Receptor with the Receptor Knockout Mice

催产素受体（OXTR）被认为是生殖生理和社会性行为的关键。然而，Oxt缺陷（Oxt-/-）小鼠仅在泌乳和社会识别方面表现出缺陷。为了分析OXTR在生殖和中枢神经系统中的作用，我们培育了缺乏OXTR基因（OXTR -/-）的小鼠。Oxtr-/-小鼠表现出正常的交配率、怀孕率和产仔数，这表明Oxtr对雄性或雌性生殖功能都不是必需的。虽然Oxtr-/-雌性在分娩时没有表现出明显的缺陷，但Oxtr-/-雌性的后代在出生后全部死亡。产后oxr -/-女性乳腺的组织学分析表明，乳腺导管积聚了乳汁。产后雄性/雌性表现出母性行为障碍。纯Oxtr-/-雌性表现出类似的表型，这表明Oxtr是在生理之外对幼崽的养育反应所必需的。我们观察到，与只饲养Oxtr+/+小鼠的笼子相比，成群饲养的雄性小鼠在含有Oxtr-/ +小鼠的笼子中受伤的数量更多，我们使用常驻入侵者测试来评估攻击行为。Oxtr-/-小鼠表现出较高的攻击行为。然而，血浆睾酮浓度在Oxtr+/+和Oxtr-/-小鼠之间没有显著差异。相比之下，在含有Oxt敲除（Oxt-/-）雄鼠的笼子中，受伤小鼠的比例与Oxt+/+小鼠相似。此外，在常驻入侵者测试中，Oxt-/-小鼠的攻击行为与Oxt+/+小鼠没有区别。这种在Oxt-/和Oxt-/-小鼠之间的攻击表型差异可能暗示了Oxt-/-小鼠中Oxtr的不依赖于Oxt的激活。< OTR的其他功能>雄性OTR /-小鼠在15周龄时出现肥胖，而雌性则没有。雄性小鼠脂肪组织组织学分析显示，性腺白色脂肪组织（WAT）中脂质聚集，棕色脂肪组织（BAT）中大部分细胞充满大脂滴，显示出典型的产热功能障碍特征。当其他小鼠暴露在寒冷环境中时，它们的直肠温度迅速下降。BAT的冷敏感多伴有不能诱导产热机制。在其他-/-小鼠中，与野生型动物相比，BAT中α2与β3肾上腺素能受体（ARs）的表达比例发生了改变。由于α 2和β3 ar在产热方面具有相反的作用，因此这些ar的不平衡可能会减少能量消耗并减少产热，从而可能导致肥胖。少

The oxytocin receptor (OXTR) has been considered to be essential for reproductive physiology and sociosexual behaviors. However, OXT-deficient (Oxt-/-) mice displayed defects only in milk ejection and social recognition. To analyze the roles of the OXTR in the reproductive and central nervous systems, we generated mice lacking the Oxtr gene (Oxtr-/-). <Reproductive Function> Oxtr-/-mice exhibited normal rates of mating, pregnancy, and litter sizes, demonstrating that OXTR is not essential for either male or female reproductive function. Although Oxtr-/-females showed no obvious defect in parturition, all offspring of Oxtr-/-females died after birth. Histological analysis of mammary glands in postpartum Oxtr-/-females indicated that ducts accumulated milk. <Sociosexual Behavior> Postpartum Oxtr-/-females displayed the impairment of maternal behavior. Virgin Oxtr-/-females displayed a similar phenotype, suggesting that OXTR is required for nurturing responses to pups outside the physiolo … More gical context of pregnancy and parturition. We observed more wounded mice in group-housed males from cages containing Oxtr-/-mice than in cages containing only Oxtr+/+ mice, we assessed aggressive behavior using the resident-intruder test. Oxtr-/-mice showed elevated aggressive behavior. However, plasma testosterone concentrations were not significantly different between Oxtr+/+ and Oxtr-/-mice. In contrast, in cages containing OXT-knockout (Oxt-/-) males, the rate of wounded mice was similar to that in Oxt+/+ mice. Furthermore, aggressive behavior of Oxt-/-mice in the resident-intruder test was indistinguishable from Oxt+/+ mice. This discrepancy in aggression phenotypes between Oxtr-/-and Oxt-/-mice potentially implicates OXT-independent activation of OXTR in Oxt-/-mice. <Other function of OTR> Male otr-/-mice developed obesity by 15 week old but female did not. Histlogical analysis of adipose tissue in male otr-/-mice showed lipid accumulation in gonadal white adipose tissue (WAT), and most of cells in brown adipose tissue (BAT) were filled with large lipid droplets, suggesting a typical feature in dysfunction of thermogenesis. When otr-/-mice were exposed to cold, their rectal temperature dropped rapidly. Cold-sensitive was mostly accompanied by failure to induce thermogenic mechanism in BAT. In otr-/-mice, the ratio of α2 to β3 adrenergic receptors (ARs) expressing in BAT was altered in comparison with that in wildtype animals. As α 2 and β3 ARs were known to have opposite effects in thermogenesis, the inbalance of these ARs might attenuate energy expenditure accompanied with less thermogenesis, possibly leading to obesity. Less