|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 1999 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1998 : ¥2,000,000 (Direct Cost : ¥2,000,000)
1. We obtained homozygous NMB-R deficient mice in which genetic background was closer to C57BL/6 mice strain. We demonstrated inactivation of NMB-R in these knock-out mice brain by showing absence of normal NMB-R transcript and lack of ligand binding.
2. Sugar and hormonal concentration levels in the blood, such as insulin, prolactin and gastrin were normal as compared as control wild type mice.
3. Reflex, motor activity, sense or cognitive ability were normal.
4. We could not detect any morphological abnormalities in brain and gastrointestinal tissues, the sites of NMB-R expressions in normal mice, by examining tissue sections processed with normal histological stainings. Moreover, immunohistochemical analysis revealed that expressions of CRF, oxytocin, arginine-vasopressin, LHRH, GRP, Neuropeptide Y, tyrosin hydroxylase, somatostain, Ach, Enk, substance P were comparable to control mormal mice.
5. In NMB-R-deficient mice, expression of serotonin (5-HT) in dorsal raphe neurons was enhanced. After restraint stress, increase in serotonin expression in these neurons was smaller in NMB-R-deficient mice than normal mice, indicating altered response to stress. In addition, number of c-Fos expressing cells in hypothalamic paraventricular nucleus was augmented in NMB-R-deficient mice in non-stressed condition. These mutant mice showed increased time of immobolity in the forced swimming test, indicating abnormal behavioral response to stress.
6. Administration of NMB or GRP in these NMB-R-deficient mice in vivo, or in vitro demonstrated that NMB/NMB-R system has important role in thermoregulation but may not be concerned in smooth muscle contraction of gastric tissue or inhibition of food intake.