Discoidin Domain Receptor 2 (DDR2) Is Required for Maintenance of Spermatogenesis in Male Mice
Discoidin Domain Receptor 2 (DDR2) Is Required for Maintenance of Spermatogenesis in Male Mice
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DOI：
10.1002/mrd.21093
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发表时间：
2010-01-01
影响因子：
2.5
通讯作者：
Naito, Kunihiko
中科院分区：
文献类型：
--
作者：
Kano, Kiyoshi;Kitamura, Ayami;Naito, Kunihiko
盘状蛋白结构域受体2 （DDR2）是酪氨酸激酶（RTK）的一种受体。我们最近发现了纯合小突变小鼠（BKS.HRS）。Ddr2（slie/slie)/J, Ddr2（slie/slie）突变体），缺乏功能的Ddr2。Ddr2（slie/slie）突变小鼠由于外周内分泌系统失调而矮化和不育。为了了解DDR2信号在精子发生中的作用，我们研究了野生型和DDR2 （slie/slie）突变小鼠在10周龄和5月龄时几种与精子发生相关的受体、酶和蛋白质的表达。DDR2在成年野生型雄性小鼠间质细胞中表达。Ddr2（slie/slie）突变小鼠精液中分化精子的数量明显低于野生型小鼠。5个月大的Ddr2（slie/slie）突变体中tunel阳性细胞的数量显著增加。睾酮在5个月大时显著降低，但两种类型的小鼠在10周龄和5个月大时的LH相似。两种小鼠10周龄时LH受体（Lhcgr）、StAR、P450scc和Hsd3 β 6的表达水平有显著差异，而5月龄时Ddr2（slie/slie）突变体与同龄野生型小鼠相比表达水平显著降低。DDR2在成年野生型雄性小鼠间质细胞中表达。总之，我们的研究结果表明，DDR2信号在维持男性精子发生中起着关键作用。
Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase (RTK). We recently identified homozygous smallie mutant mice (BKS.HRS. Ddr2(slie/slie)/J, Ddr2(slie/slie) mutants), which lack a functional DDR2. Ddr2(slie/slie) mutant mice are dwarfed and infertile due to peripheral dysregulation of the endocrine system. To understand the role of DDR2 signaling in spermatogenesis, we studied the expression of several receptors, enzymes, and proteins related to spermatogenesis in wild-type and Ddr2(slie/slie) mutant mice at 10 weeks and 5 months of age. DDR2 were expressed in adult wild-type male mice in Leydig cells. The number of differentiated spermatozoa in the seminal fluid was significantly lower in the Ddr2(slie/slie) mutant mice than in the wild-type mice. The number of TUNEL-positive cells was significantly greater in 5-month-old Ddr2(slie/slie) mutants. Testosterone was significantly reduced at 5 months age, but LH was similar in both types of mice at both 10 weeks and 5 months of age. The expression levels of LH receptors (Lhcgr), StAR, P450scc, and Hsd3 beta 6 were significantly different between the two types of mice at 10 weeks of age, but they were significantly reduced in 5-month-old Ddr2(slie/slie) mutants compared to wild-type mice of the same age. DDR2 was expressed in the Leydig cells of adult wild-type male mice. In conclusion, our results indicated that DDR2 signaling plays a critical role in the maintenance of male spermatogenesis.