Structure of the Mouse Gonadotropin-Releasing Hormone Receptor Gene: Variant Transcripts Generated by Alternative Processing

The mouse gonadotropin-releasing hormone receptor (GnRHR) is unique among G-protein-coupled receptors in its lack of a putative intracellular carboxy-terminal domain. A gonadotrope cell line cDNA library was screened in a search for alternative forms of the receptor transcript and 42 clones were obtained, representing a number of variant cDNAs. To determine the origin of these transcripts, the structure of the mouse gene was mapped from 11 distinct genomic clones. The gene contains three exons, spanning more than 22 kb. Exons 1, 2, and 3 encode, respectively, nucleotides +1 to +522, +523 to +739, and +740 to +981 of the open reading frame of the cDNA for the functional mouse GnRHR. Southern blot analysis with genomic DNA is consistent with the presence of a single gene. By comparison with the genomic sequence, the origins of the variant cDNAs isolated can be clarified. All the cDNAs contain the first exon and the majority (71%) encode the functional 327-amino-acid receptor previously reported. One group of clones (14%), which contains exons 1 and 2, continues 700 bp past the exon 2 splice donor of the wild-type receptor. These clones terminate after a polyadenylation signal and have an open reading frame encoding a protein of only 261 amino acids. In a different group of transcripts (5%), exon 2 is absent, resulting in a shift in the reading frame and encoding a protein of 177 amino acids. These data support alternative processing of the mouse GnRHR gene.