The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development
The hotei mutation of medaka in the anti-Mullerian hormone receptor causes the dysregulation of germ cell and sexual development
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DOI：
10.1073/pnas.0611379104
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发表时间：
2007-06-05
影响因子：
11.1
通讯作者：
Kondoh, Hisato
中科院分区：
文献类型：
--
作者：
Morinaga, Chikako;Saito, Daisuke;Kondoh, Hisato
我们以前在青鳉中进行了性腺发育缺陷的突变体筛选，并在这方面确定了一个感兴趣的突变体，命名为hotei（热）。该突变体表现出许多显著的表型异常，包括：（i）无论鱼的遗传性别如何，生殖细胞在孵化期左右开始过度增殖;（ii）在表型雄性热纯合子中开始过早减数分裂;一半的热纯合子XY鱼经历性别逆转，其伴随雌性特征芳香酶基因在性腺体细胞中的表达;和（iv）在表型雌性纯合子中，卵泡发育在早期阶段被阻止。我们还进行了遗传作图，染色体步移，和候选基因测序分析的热，并表明，潜在的突变发生在最近发现的青鳉抗苗勒管激素（AMH）受体II型（AMHR II）基因。此外，该基因被发现是负责每一个热表型，作为amhrII转基因挽救这些异常。此外，amhr II基因在两性性腺的体细胞中表达。热纯合子的表型表明AMH/AMHR II信号系统在性腺发育中具有多种调节功能，包括对生殖细胞增殖和卵泡发育的性别依赖性调节。这些推测代表AMH的基本作用，这之前的苗勒管在胚胎发育过程中的演变。
We previously performed mutant screens in the medaka for defects in gonadal development and identified a mutant of interest in this regard, which was designated as hotei (hot). This mutant manifests a number of remarkable phenotypic abnormalities including: (i) excessive proliferation of germ cells that initiates at around the hatching stage regardless of the genetic sex of the fish; (it) initiation of premature meiosis in phenotypically male hot homozygotes; (fit) one-half of the hot-homozygous XY fish undergo sex reversal, which accompanies the expression of the female-characteristic aromatase gene in the somatic cells of the gonad; and (iv) in phenotypically female homozygotes, follicular development is arrested at an early stage. We have also performed genetic mapping, chromosome walking, and candidate gene sequencing analysis of hot and demonstrate that the underlying mutation occurs in the recently identified medaka anti-Mullerian hormone (Amh) receptor type II (amhrII) gene. Moreover, this gene was found to be responsible for each of the hot phenotypes, as an amhrII transgene rescues these abnormalities. in addition, the amhrII gene is expressed in the somatic cells of the gonads of both sexes. The phenotypes of the hot homozygotes indicate that there are multiple regulatory functions of the AMH/AMHRII signaling system in the development of the gonad, including the sex-dependent regulation of germ cell proliferation and follicular development. These presumably represent the basic roles of Amh, which precede Mullerian duct evolution during phylogeny.