B219/OB-R 5 '-UTR and leptin receptor gene-related protein gene expressionin mouse brain and placenta: Tissue-specific leptin receptor promoter activity

Leptin receptor (OB-R) splice variants either encode proteins with differen t 3' cytoplasmic domains or have different 5' untranslated regions (UTR), i ndicative of dual promoters. The B219/OB-R promoter transcribes only OB-R t ranscripts, whereas the OB-R/GRP promoter initiates transcription of both O B-R and another protein of unknown function, called the leptin receptor gen e-related protein (OB-RGRP). We compared expression of B219/OB-R 5'-UTR and OB-RGRP mRNAs by in situ hybridization. We thus assessed, by inference, th e contributions of the two promoters to the leptin receptor transcript pool , in murine brain or in placenta, a tissue with abundant leptin receptor mR NA. Expression of B219/OB-R 5'-UTR mRNA (and thus by inference B219/OB-R pr omoter activity) in brain was similar in both distribution and relative int ensity to OB-R mRNA. OB-RGRP mRNA (and thus by inference OB-R/GRP promoter activity) was widely distributed in murine brain, with elevated expression in the hypothalamic regions that express the leptin receptor mRNA, includin g the paraventricular nucleus. B219/OB-R 5'-UTR mRNA, but not OB-RGRP mRNA, was upregulated in hypothalamus of obese ob/ob mice. In placenta, B219/OB- R 5'-UTR mRNA was restricted to the maternal interface, and transcription o f both long and short leptin receptor splice variants in the main body of t he tissue thus proceeds via the OB-R/GRP promoter, strongly indicative of t issue-specific promoter usage.