Functional Analysis of Oxytocin Receptor with the Receptor Knockout Mice

催产素受体被认为是生殖生理和社会性行为所必需的。然而，oxt缺陷(oxt-/-)小鼠只在排奶和社会认知度方面有缺陷。为了分析OXTR在生殖和中枢神经系统中的作用，我们产生了缺失OXTR基因的小鼠(OXTR-/-)。&lt；生殖功能&gt；Oxtr-/-小鼠表现出正常的交配率、妊娠率和产仔数，表明Oxtr对雄性或雌性生殖功能都不是必需的。虽然OXTR-/-雌性在分娩过程中没有明显的缺陷，但其后代在出生后全部死亡。产后OXTR-/-女性乳腺的组织学分析表明，导管积累了乳汁。产后社会性行为和产后OXTR-/-女性表现出母性行为的损害。处女Oxtr-/-雌性表现出类似的表型，这表明Oxtr是培养对Physiolo…以外幼崽的反应所必需的关于怀孕和分娩的更一般的背景。我们观察到，与只有OXTR+/+小鼠的笼子相比，在包含OXTR-/-小鼠的笼子中，群养雄性小鼠受伤的小鼠更多，我们使用常驻入侵者测试来评估攻击行为。OXTR-/-小鼠表现出更高的攻击行为。然而，OXTR+/+和OXTR-/-小鼠之间的血浆睾酮浓度没有显著差异。相反，在包含oxt基因敲除(oxt-/-)雄鼠的笼子中，受伤小鼠的比率与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。Oxtr-/-和oxt-/-小鼠在攻击表型上的差异潜在地暗示了oxt-/-小鼠中Oxtr的非依赖激活。Otr&gt；雄性Otr-/-小鼠的其他功能在15周龄时出现肥胖，而雌性没有。雄性Otr-/-小鼠脂肪组织的组织学分析显示，性腺白色脂肪组织(WAT)内脂肪堆积，棕色脂肪组织(BAT)内多数细胞内充满大的脂滴，这是产热功能障碍的典型特征。当OTR-/-小鼠暴露在寒冷中时，它们的直肠温度迅速下降。在BAT中，冷敏感大多伴随着不能诱导生热机制。在OtR-/-小鼠中，α-2/β-3肾上腺素能受体(AR)在BAT中的表达比野生型动物有所改变。由于α-2和β-3受体在产热过程中具有相反的作用，这两种受体的失衡可能会减少能量消耗，减少产热，从而可能导致肥胖。较少

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