Characterization of a novel satiety peptide, mDP1, that was cloned from the TRH knockout mice.

2007 Fiscal Year Final Research Report Summary

• Project/Area Number: 17590953
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Gunma University
• Principal Investigator: YAMADA Masanobu Gunma University, school of Medicine, Associate Professor (90261833)
• Project Period (FY): 2005 – 2007
• Keywords: TRH / mDP1 / Knockout mice

Research Abstract

TRH has been reported to possess several neurophysiological actions in the brain. To gain insights into the molecular mechanisms underlying these effects, we attempted to clone a cDNA that was regulated by TRH using TRH knockout mice and subtractive cDNA analysis and a microarray system. Over 100 clones obtained by these analyses between the wild-type and TRH^<-/->cerebellum were analyzed. Among them, a clone, mDP1 mRNA level in the euthyroid TRH^<-/-> cerebellum supplemented with thyroid hormone were significantly decreased compared with those in the wild-type. Northern blot analysis of seven brain regions including hypothalamus, striatum, midbrain hippocampus, pons, cerebellum, and cortex revealed that mDP1 mRNA were expressed significantly in the hypothalamus and cerebellum. Furthermore, starvation for 72 hours lead to a significant decrease in mDP1 mRNA level in the hypothalamus and cerebellum. These results suggested that mDP1 might be a substance for regulating satiety behavior.
We recently established mDP1 knockout (mDP1KO) mice using a homologous recombination in ES cells. We first confirmed that mRNA and protein for mDP1 were completely deleted in mDP1KO mice using Northern blot analysis and Western blot analysis. These mDP1KO mice were normally born and grew up. However, mDP1KO mice were resistant to diet-induced obesity, and showed low serum triglyceride and cholesterol levels.