| Co-Investigator(Kenkyū-buntansha) |
YOKOMORI Kinji Japan Red Cross Medical Center, Department of Pediatric Surgery, Department Head, 小児外科, 部長 (20251291)
KURIHARA Hiroki University of Tokyo, Department of Internal medicine, Assistant, 医学部付属病院, 助手 (20221947)
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| Research Abstract |
Five methods were developed to avoid difficulties from juvenile lethality or growth retardation in knockout mice and to study circulatory, respiratory, and autonomic functions in them : to make medulla-spinal cord preparation from newborn mice, a way to rescue newborn pups with tracheotomy, special small devices to measure blood pressure and respiratory mechanics, construction of artificial anus, and genetic rescue. These methods were applied to endothelin (ET) -1 knockout mouse, ET-A receptor (ETAR) knockout mouse, ET-B receptor (ETBR) knockout mouse, and insulin receptor substrate-1 (IRS-1) knockout mouse. Medulla-spinal cord preparation from ET-1 knockout mice and tracheotomized newborn mice of ET-1 knockout and ETAR knockout showed severe attenuation of respiratory reflex to hypercapnia. Endogenous ET-1-ETAR system thus physiologically participates in the central chemosensitivity. In genetically established mutant mice in which ETBR was 1/8 of normal mice, arterial blood pressure (AP) was elevated with normal sympathetic activity and respiration. The result is consistent with a pressor response to selective blockade of ETBR in normal mice. Thus, ETBR contribute physiologically to diminish basal level of AP through peripheral mechanism. IRS-1 knockout mice showed growth retardation and elevation of AP.Thus IRS-1 is also essential to maintain normal AP.In conclusion, knockout mice are a valuable research resource especially in the study of integrative physiological functions of mammals.
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