Transgenic Mice Overexpressing Ghrelin or Ghrelin Analog

To understand the chronic effects of ghrelin, genetically engineered mouse models would be useful. Early studies, however, suggested that it was challenging to generate ghrelin gain-of-activity models by standard procedures. Although several groups have been trying to generate transgenic (Tg) mice overexpressing ghrelin, almost all these animals produced only des-acyl ghrelin rather than acylated ghrelin. Therefore, to elucidate the mechanism for the fatty acid modification in ghrelin, many researchers have been seeking an enzyme that would catalyze the acylation of ghrelin with an octanoic acid. In 2008, ghrelin O-acyltransferase (GOAT) was identified at last, and thereafter double-Tg mice overexpressing ghrelin and GOAT were generated by Kirchner et al. On the other hand, we have succeeded in generating Tg mice overexpressing Trp(3)-ghrelin, a ghrelin analog that does not require posttranscriptional modification with GOAT for activity. These ghrelin gain-of-activity models are useful tools for evaluating the long-term pathophysiological and/or pharmacological effects of ghrelin or ghrelin analogs and provide insight into the physiological roles of ghrelin/GHS-R systems.