Müllenbach Eike, Walter Lutz, Dressel Ralf
University of Göttingen, Department of Immunogenetics, Göttingen, Germany.
Gene. 2006 May 10;372:53-61. doi: 10.1016/j.gene.2005.12.004. Epub 2006 Feb 9.
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.
编码盘状结构域受体1（DDR1）的Ddr1基因是受体酪氨酸激酶小亚家族的成员之一，已知其参与细胞分化、增殖和细胞黏附。细胞外盘状结构域负责与配体胶原蛋白结合。作为人类同源物，大鼠Ddr1基因由17个外显子组成，位于主要组织相容性复合体，即大鼠的RT1复合体中。本文描述了一种新的3.5 kb睾丸特异性Ddr1转录本，其在大鼠睾丸减数分裂后的生殖细胞中特异性表达。该转录本缺失外显子1至5，推测的蛋白质将缺乏盘状结构域和部分柄区。全长4.3 kb和新的3.5 kb Ddr1转录本的表达水平均取决于RT1单倍型。在DA和LEW.1AV1大鼠携带的RT1(avl)单倍型中，3.5 kb Ddr1转录本完全缺失。这可能是由于RT1(avl)单倍型中缺少四个核苷酸GGGC，这四个核苷酸似乎在3.5 kb Ddr1转录本假定的睾丸特异性可变启动子区域的Ddr1基因内含子5中形成了一个SP1结合位点。此外，在Ddr1基因的5'非翻译区发现了两个新的外显子，它们产生了更多可变的Ddr1转录本。有趣的是，3.5 kb Ddr1转录本不仅在减数分裂后的生殖细胞中以细胞类型特异性方式表达，还受RT1单倍型的控制。
