STRUCTURE AND REGULATION OF THE MOUSE MELANIN-CONCENTRATING HORMONE MESSENGER-RNA AND GENE

Melanin-concentrating hormone (MCH) and associated peptides, designated NEI and NGE, are predominantly expressed in hypothalamic neurons which project widely throughout the mammalian brain. These peptides might be involved as neuromodulators in the control of goal-directed behaviors, the integration of the stress response, and/or the regulation of arousal in general. In vivo studies of this peptidic system using a transgenic mouse model call for information about the structure and regulation of the mouse MCH (mMCH) gene. One complementary DNA (cDNA) for mouse prepro-MCH was isolated from a brain library by using a rat MCH cDNA as probe. This cDNA contains an open reading frame coding for a 165-amino acid precursor that displays about 90% sequence identity with rat and human prepro-MCHs. Most of the structural portion of the mMCH gene was cloned and characterized using the polymerase chain reaction (PCR). Strong conservation in exon-intron organization and primary sequences was found among the mouse, rat, and human genes, suggesting that coding and noncoding regions have important biological functions. Developmentally regulated expression of mMCH gene in mouse hypothalamus was examined by Northern blot hybridization. Up to 10-fold changes in the relative mMCH mRNA contents were observed during postnatal development, characterized by a peak at the weaning period. Moreover, striking variations in mMCH mRNA length, due to a poly(A) tail, were revealed during postnatal life. Tissue distribution of mMCH gene transcripts was investigated by means of the PCR and Northern blot procedures. Expression of the mMCH gene was revealed in heart, intestine, spleen, and testis and was found to be regulated in a developmentally programmed manner. Strikingly, short as well as long mMCH RNA species were identified at the periphery. Taken together, our data indicate that both transcriptional and post- transcriptional mechanisms regulate the expression of the MCH gene in mouse brain and at the periphery. © 1993 Academic Press Inc.