Molecular Cloning of the Mouse Follicle-Stimulating Hormone Receptor Complementary Deoxyribonucleic Acid: Functional Expression of Alternatively Spliced Variants and Receptor Inactivation by a C566T Transition in

The gonadotropin receptors, i.e., those of LH and FSH (FSHR), are pivotal elements in the regulation of gonadal func-tion. Recently, extensive efforts have been made to elucidate the structure-function relationship of these receptors as well as the modulatory mechanism(s) of their function. In the present study, we report 1) characterization of the mouse (m) FSHR cDNA coding sequence and 2) the functional consequences of coex-pression of several splice variants of the mFSHR. In addition, we evaluate 3) the impact on mFSHR function of a C566T transition in exon 7 of the coding sequence, a substitution analogous to the inactivating mutation in the human FSHR gene responsible for a hereditary form of hypergonadotropic ovarian failure. Mo-lecular cloning of the mFSHR cDNA was carried out by reverse transcription-polymerase chain reaction (RT-PCR) using 129/Sv mouse testicular RNA and primers complementary to the rat or the partially characterized mouse FSHR sequence. Overlapping partial fragments of receptor cDNA were amplified, sequenced, and engineered to produce the entire cDNA coding sequence, subcloned into the pSG5 expression vector. Using a similar ap-proach, 4 different receptor splice variants, selectively lackin