Cloning and characterization of a novel neuropeptide using TRH knockout mice.

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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.