Absence of the prion protein homologue Doppel causes male sterility
Absence of the prion protein homologue Doppel causes male sterility
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DOI：
10.1093/emboj/cdf386
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发表时间：
2002-07-15
期刊：
影响因子：
11.4
通讯作者：
Aguzzi, A
中科院分区：
文献类型：
--
作者：
Behrens, A;Genoud, N;Aguzzi, A
导致普恩病毒疾病的病原体被认为与PrPSc相同，PrPSc是正常的普恩蛋白PrPC的构象。PrPC缺陷小鼠不会表现出主要的病理变化，可能是因为它们表达一种名为DPL的蛋白质，这种蛋白质与PrPC在生化和结构上有显著的同源性。为了研究DPL的生理功能，我们产生了编码DPL的PrND基因纯合子破坏的小鼠。DPL缺乏不会影响胚胎和出生后的发育，但会导致男性不育。DPL蛋白在精子发生后期表达，DPL突变体的精子细胞数量减少，不能活动，畸形，不能体外受精。机械解剖透明带部分恢复体外受精。我们的结论是，DPL通过控制雄配子发生和精子-卵子相互作用的几个方面来调节雄性生育。
The agent that causes prion diseases is thought to be identical with PrPSc, a conformer of the normal prion protein PrPC. PrPC-deficient mice do not exhibit major pathologies, perhaps because they express a protein termed Dpl, which shares significant biochemical and structural homology with PrPC. To investigate the physiological function of Dpl, we generated mice harbouring a homozygous disruption of the Prnd gene that encodes Dpl. Dpl deficiency did not interfere with embryonic and postnatal development, but resulted in male sterility. Dpl protein was expressed at late stages of spermiogenesis, and spermatids of Dpl mutants were reduced in numbers, immobile, malformed and unable to fertilize oocytes in vitro. Mechanical dissection of the zona pellucida partially restored in vitro fertilization. We conclude that Dpl regulates male fertility by controlling several aspects of male gametogenesis and sperm-egg interaction.