A novel discoidin domain receptor 1 (Ddr1) transcript is expressed in postmeiotic germ cells of the rat testis depending on the major histocompatibility complex haplotype

Abstract

The Ddr1 gene encoding the discoidin domain receptor 1 (DDR1), a member of a small subfamily of receptor tyrosine kinases, is known to be involved in differentiation, proliferation, and cell adhesion. The extracellular discoidin domain is responsible for the binding of the ligand collagen. As the human homologue, the rat Ddr1 gene consists of 17 exons and is located in the major histocompatibility complex, the RT1 complex in rats. A novel testis-specific Ddr1 transcript of 3.5 kb is described here which is expressed specifically in the postmeiotic germ cells of the rat testis. The exons 1 to 5 are missing in this transcript and the putative protein would lack the discoidin domain and parts of the stalk region. The expression level of both, the full-length 4.3 kb and the novel 3.5 kb Ddr1 transcript, is dependent on the RT1 haplotype. In the RT1(avl) haplotype, carried by DA and LEW.1AV1 rats, the 3.5 kb Ddr1 transcript is completely missing. This might be explained by the lack of four nucleotides GGGC in the RT1(avl) haplotype, which appear to contribute to a SP1 binding site in intron 5 of the Ddr1 gene in the presumed testis-specific alternative promoter region of the 3.5 kb Ddr1 transcript. In addition, two novel exons in the 5'-untranslated region of the Ddr1 gene were found that give rise to further alternative Ddr1 transcripts. Interestingly, the 3.5 kb Ddr1 transcript is not only expressed in a cell type-specific manner in postmeiotic germ cells but also controlled by the RT1 haplotype.