Publications (3)45.48 Total impact
Nature 12/1997; 390(6660):618-622. · 36.28 Impact Factor
Article: Bronchial hyperreactivity, increased endotoxin lethality and melanocytic tumorigenesis in transgenic mice overexpressing platelet-activating factor receptor[show abstract] [hide abstract]
ABSTRACT: Although platelet-activating factor (PAF) has been shown to exert pleiotropic effects on isolated cells or tissues, controversy still exists as to whether it plays significant pathophysiological roles in vivo. To answer this question, we established transgenic mice overexpressing a guinea-pig PAF receptor (PAFR). The transgenic mice showed a bronchial hyperreactivity to methacholine and an increased mortality when exposed to bacterial endotoxin. An aberrant melanogenesis and proliferative abnormalities in the skin were also observed in the transgenic mice, some of which spontaneously bore melanocytic tumors in the dermis after aging. Thus, PAFR transgenic mice proved to be a useful model for studying the basic pathophysiology of bronchial asthma and endotoxin-induced death, and screening of therapeutics for these disorders. Furthermore, our findings provide new insights regarding the role of PAF in the morphogenesis of dermal tissues as well as the mitogenic activity of PAF and PAFR in vivo.The EMBO Journal 12/1996; 16(1):133-142. · 9.20 Impact Factor
Article: Inhibition of pancreatic β-cell glucokinase by antisense RNA expression in transgenic mice: mouse strain-dependent alteration of glucose tolerance[show abstract] [hide abstract]
ABSTRACT: We have generated transgenic mice, in either C57BL/6 or C3H background, expressing antisense glucokinase mRNA in β-cells. The glucose phosphorylating activity at 60 mM glucose in transgenic islets was significantly lower than that in controls, and the insulin secretory response to glucose was lower in transgenic islets than in those of controls in both strains. Following i.p. glucose challenge, higher blood glucose levels were observed in transgenic mice than in controls in the C57BL/6 nut not the C3H background. These data suggest that a β-cell secretory defect, in combination with other undefined genetic factors, causes impaired glucose homeostasis in mice.FEBS Letters.