| Budget Amount *help |
¥14,600,000 (Direct Cost: ¥14,600,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2003: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2002: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Research Abstract |
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
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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
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