Splice variants of the OB receptor gene are differentially expressed in brain and peripheral tissues of mice

A high affinity receptor for OB protein was recently cloned from the choroid plexus of mice. At least six alternatively spliced forms of the OB receptor (OBR) gene have been described, all of which encode proteins containing the OB-R extracellular domain. One splice variant encodes a receptor with a long intracellular domain, OB-R-L, that has been implicated in OB-R signaling. Here, we have used in situ hybridization to examine the localization-of OB-R splice variants in brain and peripheral tissues of adult and newborn mice. Using a probe hybridizing with all known splice variants, we confirmed that OB-R mRNA was widely distributed in the adult tissues. In the CNS, choroid plexus was the major site of expression. We now demonstrate that OB-R mRNA is expressed in peripheral tissues; primarily associated with connective tissues. In addition, OBR mRNA was detected at higher levels in peripheral tissues of newborn mice than in adult mice. With a probe specific for OB-R-L, we confirmed that high mRNA expression was detected in hypothalamic nuclei, while low levels were observed in choroid plexus. We now report that in peripheral tissues of adult mice, OB-R, mRNA expression was either very low or undetectable. In newborn mice, the pattern of OB-R, message expression in the CNS was similar to that of adult mice, while bone was the site of highest OB-R, message expression in the peripheral tissue. These data suggest different biological roles for OB-R splice variants encoding the shea and long forms of OB-R. The localization of OB-R-L to hypothalamic nuclei supports the idea that OB-R-L is the brain receptor that mediates OB protein signaling and actions. In addition, the expression of OB-R message in newborn mice also suggests a biological role of OB-R during development in mice.