OAZ-t/OAZ3 is essential for rigid connection of sperm tails to heads in mouse.
OAZ-t/OAZ3 is essential for rigid connection of sperm tails to heads in mouse.
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OAZ-T/OAZ3对于将精子尾巴与鼠标头部的刚性连接至关重要。
DOI：
10.1371/journal.pgen.1000712
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发表时间：
2009-11
期刊：
影响因子：
4.5
通讯作者：
Tanaka H
中科院分区：
文献类型：
--
作者：
Tokuhiro K;Isotani A;Yokota S;Yano Y;Oshio S;Hirose M;Wada M;Fujita K;Ogawa Y;Okabe M;Nishimune Y;Tanaka H
已知多胺在多种细胞的增殖和分化中发挥重要作用。尽管睾丸中合成并储存了大量的多胺，但它们的作用仍然未知。鸟氨酸脱羧酶抗酶（OAZ）以反馈方式控制细胞内多胺的浓度。 OAZ1 和 OAZ2 普遍表达，而 OAZ-t/OAZ3 在精子发生期间的生殖细胞中特异性表达。据报道，OAZ-t 与鸟氨酸脱羧酶 (ODC) 结合并使 ODC 活性失活。在先前的研究中，多胺能够在 OAZ-t mRNA 的移码序列处诱导移码，从而导致 OAZ-t 的翻译。为了研究 OAZ-t 的生理作用，我们培育了 OAZ-t 破坏的突变小鼠。纯合OAZ-t突变雄性小鼠不育，尽管这些小鼠的附睾和睾丸多胺浓度正常，而雌性小鼠具有生育能力。从突变小鼠的附睾中成功回收了精子，但在培养过程中，精子细胞的头部和尾部很容易在培养基中分离。结果表明，OAZ-t 对于精子发生过程中头部和尾部之间刚性连接的形成至关重要。脱落的尾巴和头都是活的，大部分无头尾巴都呈直线向前运动。尽管无尾精子未能与顶体反应，但头部能够通过胞浆内精子注射使卵子受精。 OAZ-t 可能通过局部多胺浓度在单倍体生殖细胞分化中发挥关键作用。多胺对于细胞增殖和分化至关重要，但它们在这些过程中的作用尚不清楚。鸟氨酸脱羧酶抗酶 (OAZ) 是控制细胞内多胺浓度的酶。为了阐明其中一种酶 OAZ-t 在精子形成过程中多胺浓度调节中的作用，我们培育了 OAZ-t 基因被破坏的突变小鼠。当我们观察缺乏功能性 Oaz-t 基因的小鼠的精子时，我们发现精子头部很容易与尾部分离，这表明 OAZ-t 对于精子发育过程中头部和尾部之间刚性连接的形成至关重要。许多无头尾巴可以继续游泳，但它们无法参与成功受精所需的信号传导过程。然而，当将无尾头注射到未受精卵中时，它可以产生健康的幼崽。以前从未发现过这样的表型。突变小鼠引发了罕见的不育人类患者的精子行为正常的情况。我们的研究强调了研究精子发生和受精过程的重要性。
Polyamines are known to play important roles in the proliferation and differentiation of many types of cells. Although considerable amounts of polyamines are synthesized and stored in the testes, their roles remain unknown. Ornithine decarboxylase antizymes (OAZs) control the intracellular concentration of polyamines in a feedback manner. OAZ1 and OAZ2 are expressed ubiquitously, whereas OAZ-t/OAZ3 is expressed specifically in germline cells during spermiogenesis. OAZ-t reportedly binds to ornithine decarboxylase (ODC) and inactivates ODC activity. In a prior study, polyamines were capable of inducing a frameshift at the frameshift sequence of OAZ-t mRNA, resulting in the translation of OAZ-t. To investigate the physiological role of OAZ-t, we generated OAZ-t–disrupted mutant mice. Homozygous OAZ-t mutant males were infertile, although the polyamine concentrations of epididymides and testes were normal in these mice, and females were fertile. Sperm were successfully recovered from the epididymides of the mutant mice, but the heads and tails of the sperm cells were easily separated in culture medium during incubation. Results indicated that OAZ-t is essential for the formation of a rigid junction between the head and tail during spermatogenesis. The detached tails and heads were alive, and most of the headless tails showed straight forward movement. Although the tailless sperm failed to acrosome-react, the heads were capable of fertilizing eggs via intracytoplasmic sperm injection. OAZ-t likely plays a key role in haploid germ cell differentiation via the local concentration of polyamines. Polyamines are essential for cell proliferation and differentiation, but their role in these processes is unknown. Ornithine decarboxylase antizymes (OAZs) are enzymes that control the concentration of polyamines in cells. To elucidate the role of one of these enzymes, OAZ-t, in the regulation of polyamine concentration during sperm formation, we generated mutant mice in which the OAZ-t gene was disrupted. When we observed sperm from the mice lacking a functional Oaz-t gene, we found that the sperm heads separated easily from the tails, indicating that OAZ-t is essential for the formation of a rigid junction between the head and tail during sperm development. Many of the headless tails could continue swimming, but they were unable to participate in the signaling processes required for successful fertilization. However, tailless heads could produce healthy pups when injected into unfertilized eggs. Such a phenotype has not been previously found. The mutant mice evoked rare cases of infertile human patients whose sperm behaves in a proper fashion. Our study underscores the importance of research into the processes of spermatogenesis and fertilization.
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影响因子：
3.6
作者：
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通讯作者：
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DOI：
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DOI：
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发表时间：
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影响因子：
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作者：
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