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the 19th letter of the Roman alphabet (同)s

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sulfurの化学記号 / {略}South[ern]

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/10/01 08:59:28」(JST)

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この項目では、哺乳類の性決定遺伝子SRYについて説明しています。他の生物で性別を決定する遺伝子については「性決定#遺伝子機構」をご覧ください。

SRY（Sex-determining region Y）とは哺乳類のY染色体上にあり、胚の性別を雄に決定する遺伝子^[1]^[2]^[3]である。哺乳類特有の性決定遺伝子であり他の生物ではアフリカツメガエルのDM-W^[4]、メダカのDMY^[5]のように別の遺伝子が性決定に関与する。

"Sex-determining region Y"を日本語に翻訳すると「Y染色体性決定領域遺伝子」となるが、通常SRYまたはSRY遺伝子と表記する。翻訳産物であるSRYタンパク質は遺伝子本体が不明だった時代にはTDF（testis determining factor：精巣決定因子・睾丸決定因子）と呼ばれ^[6]^[7]^[8]、遺伝子が同定された後もタンパク質の呼称としてはTDF・SRY双方が使われている。

機能と構造

SRYは脊椎動物で初めて発見された性決定遺伝子である^[9]。Y染色体短腕のY染色体特異的領域に存在しており、限性遺伝する^[10]。大部分の哺乳類で雄への性決定を行う遺伝子であるが、単孔類と一部のネズミには存在しない^[11]^[12]^[13]。

機能: SRYの発現は胚の性決定のスイッチとなり、未分化の生殖腺を精巣へと誘導する。SRY自体はその後の性分化の過程には直接関わらず、精巣で作られたアンドロゲンが雄への性分化を支配する^[3]。SRYが精巣決定因子の機能を持つことは、マウスXX胚にSRY遺伝子を導入すると精巣が形成されて雄となることで確認された^[14]。; SRYが機能欠損あるいは欠失した場合、つまりSRY遺伝子に突然変異が起きて機能しない場合あるいは不等乗換えによってSRYがX染色体上に転座した場合などにはY染色体を持つ胚でも生殖腺は卵巣に分化しその個体は雌となる（スワイヤー症候群）^[15]。; 2006年に公表された論文では成熟雄ラットの神経系においてSryが発現しており、その結果、性ホルモンを介在せずに脳の性差をもたらしていることが示唆されている^[16]。
構造: SRYのDNA塩基配列はイントロンを含まず、タンパク質の構造の特徴としてHMGボックスと呼ばれるDNA結合領域を持つ^[15]。このHMGボックス構造を含みSRYと60%以上の相同性を持つ遺伝子群はSOX（SRY-related HMG box）遺伝子ファミリーと呼ばれる^[2]^[17]。SRYおよびSOXファミリーは、HMGボックスで他の遺伝子の発現制御部位のDNA配列に結合する転写因子であると考えられている^[18]^[19]。

性別判定への利用とその問題点

ヒトの性決定について性染色体の関与の判明、さらに進んでSRYの同定がなされるとそれらを用いた性別判定が行われるようになった。1960年代では、女性に特異的なX染色体ヘテロクロマチン構造（バー小体=Xクロマチン）および男性特異的なY染色体ヘテロクロマチン構造（Yクロマチン）の観察によって性別判定が行われた^[20]^[21]。

SRYが同定された後の1992年および1996年の近代オリンピックでは、SRYの存在が性別判定に用いられた。しかしながら、アメリカ合衆国の各種医療団体・学術団体はこれらの判定方法に問題があることを指摘した^[21]^[22]。その結果、2000年のオリンピック以降、SRYによる性別判定は行われていない。

上記で問題とした性染色体の存在数あるいはSRY遺伝子の存在による性別判定の不確実性は前述の「機能」の副節で触れたSRY転座 X/Y染色体による性別の逆転（XX男性・XY女性）、突然変異（1塩基欠失・1塩基置換）によるTDF機能不全SRYでは表現型が女性となることなどからもたらされている。また性分化に関与するSRY以外の遺伝子群の一部の遺伝子に突然変異がある場合も、性分化異常症をもたらすことも^[3]、上記判定法が不正確になる要因となっている。

脚注

^

遺伝子記号およびタンパク質記号の表記は、生物種ごとに異なっている（右の付表および遺伝子命名法を参照）。この記事では明らかにラット・マウスの遺伝子である場合を除いて、哺乳類Sex-determining region Y遺伝子のオーソログ全てをSRYで統一して表記する。

付表．*Sex-determining region Y* 遺伝子とタンパク質の表記
種	遺伝子記号	タンパク質記号
ヒト Homo sapiens	SRY	SRY
ラット Mus musculus マウス Rattus norvegicus	Sry	SRY

^ ^a ^b 武藤照子「哺乳類における性決定遺伝子と生殖巣の分化」（岡田益吉、長濱嘉孝、中辻憲夫編『生殖細胞の発生と性分化』）
^ ^a ^b ^c 諸橋憲一「哺乳類における生殖腺の性分化」『蛋白質核酸酵素』2004年2月号
^ Yoshimoto S, Okada E, Umemoto H, Tamura K, Uno Y, Nishida-Umehara C, Matsuda Y, Takamatsu N, Shiba T, Ito M (2008). “A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis”. Proc Natl Acad Sci USA 105: 2469-2474. doi:10.1073/pnas.0712244105 2009年5月2日閲覧。.
^ Matsuda M, Nagahama Y, Shinomiya A, Sato T, Matsuda C, Kobayashi T, Morrey CE, Shibata N, Asakawa S, Shimizu N, Hori H, Hamaguchi S, Sakaizumi M (2002). “DMY is a Y-specific DM-domain gene required for male development in the medaka fish”. Nature 417: 559-563. doi:10.1038/nature751. PMID 12037570.
^ 長井光三「哺乳動物における性決定の分子機構」『蛋白質核酸酵素』1994年8月号
^ 八杉竜一ら編「性決定物質」『岩波生物学辞典（第4版）』
^ 八杉竜一ら編「精巣決定因子」『岩波生物学辞典（第4版）』
^ Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN (1990). “A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif”. Nature 346: 216-217. doi:doi:10.1038/346240a0. PMID 1695712.
^ SRY遺伝子が発現すると雄に分化するため、厳密に言うとSRYは限性遺伝の原因となる遺伝子である。
^ 黒岩麻里「Y染色体を失った哺乳類，トゲネズミ」『生物の科学遺伝』2009年1月号
^ デイヴィッド・ベインブリッジ『X染色体：男と女を決めるもの』79-83ページ
^ Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA (2008). “Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes”. Genome Res 18: 965-973. doi:10.1101/gr.7101908 2009年5月24日閲覧。.
^ Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991). “Male development of chromosomally female mice transgenic for SRY”. Nature 351: 117-121. doi:10.1038/351117a0. PMID 2030730.
^ ^a ^b "Entrez Gene: SRY sex determining region Y" 2009年6月3日閲覧。
^ Dewing P, Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (2006). “Direct regulation of adult brain function by the male-specific factor SRY”. Curr Biol 16: 415-420. PMID 16488877.
^ アメリカ合衆国・国立生物工学情報センター（NCBI） - HomoloGene
^ 諸橋憲一「哺乳類生殖巣の分化」（岡田益吉、長濱嘉孝、中辻憲夫編『生殖細胞の発生と性分化』）
^ SOXファミリーの一部は性分化に強く関与しているものと考えられているが、その機能は哺乳類と他の生物では異なる場合もある。たとえばSOX9は哺乳類の生殖腺形成に関与しているが、鳥類では発現時期が異なるため異なる作用を持つと考えられている（諸橋憲一「哺乳類における生殖腺の性分化」『蛋白質核酸酵素』）
^ 八杉竜一ほか編「性染色質」「Yクロマチン」『岩波生物学辞典』
^ ^a ^b Elsas, LJ; Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). “Gender verification of female athletes”. Genetics in Medicine 2 (4): 249–254. PMID 11252710.
^ Dickinson, BD; Genel M, Robinowitz CB, Turner PL, Woods GL (2002). “Gender verification of female Olympic athletes”. Medicine & Science in Sports & Exercise 34 (10): 1543. PMID 12370551.

参考文献

黒岩麻里「Y染色体を失った哺乳類，トゲネズミ」『生物の科学遺伝』2009年1月号、15-19ページ、2009年、TNS。
長井光三「哺乳動物における性決定の分子機構」『蛋白質核酸酵素』1994年8月号（Vol.39 No.8）、1445-1457ページ、1994年、共立出版。
デイヴィッド・ベインブリッジ『X染色体：男と女を決めるもの』長野敬、小野木明恵（翻訳）、青土社、2004年、ISBN 978-4791761524。
武藤照子「哺乳類における性決定遺伝子と生殖巣の分化」（岡田益吉、長濱嘉孝、中辻憲夫編『生殖細胞の発生と性分化』）共立出版、478-483ページ、2000年、ISBN 978-4320055230。
諸橋憲一「哺乳類生殖巣の分化」『生殖細胞の発生と性分化』共立出版、484-490ページ、2000年。
諸橋憲一「哺乳類における生殖腺の性分化」『蛋白質核酸酵素』2004年2月号（Vol.49 No.2）、130-134ページ、2004年、共立出版。
八杉竜一ほか編「性決定」「性決定物質」「性染色質」「精巣決定因子」「Yクロマチン」『岩波生物学辞典（第4版）』岩波書店、1996年、ISBN 4-00-080087-6。

外部リンク

日本語バイオポータルサイト Jabion - SRY遺伝子情報
神戸バイオサイエンス研究会 - 第71回（2007年10月24日）：生物の雄・雌が決まる仕組みはどこまで解明されたかほか（2009年6月3日閲覧）

wiki en

[Wiki en表示]

Testis-determining factor (TDF), also known as sex-determining region Y (SRY) protein, is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in humans.^[1] SRY is an intronless sex-determining gene on the Y chromosome in the therians (placental mammals and marsupials),^[2] and mutations in this gene lead to a range of sex-related disorders with varying effects on an individual's phenotype and genotype. TDF is a member of the SOX (SRY-like box) gene family of DNA-binding proteins. When complexed with the SF1 protein, TDF acts as a transcription factor that can upregulate other transcription factors, most importantly SOX9.^[3] Its expression causes the development of primary sex cords, which later develop into seminiferous tubules. These cords form in the central part of the yet-undifferentiated gonad, turning it into a testis. The now induced Leydig cells of the testis then start secreting testosterone while the Sertoli cells produce anti-Müllerian hormone.^[4]

Gene evolution and regulation

Evolution

SRY may have arisen from a gene duplication of the X chromosome bound gene SOX3, a member of the Sox family.^[5] This duplication occurred after the split between monotremes and therians. Monotremes lack SRY and have a ZW-like sex determination system, likely involving DMRT1, whereas therians (marsupials and placental mammals) use the XY sex determination system.^[6] SRY is a rapidly evolving gene and its regulation has been difficult to study because sex determination is not a highly conserved phenomenon within the animal kingdom. ^[7]

Regulation

SRY gene has little in common with sex determination genes of other model organisms, and mice are the main model research organisms that can be utilized for its study . Understanding its regulation is further complicated because even between mammalian species, there is little protein sequence conservation. The only conserved group between mice and mammals is the High-mobility Group (HMG) box region that is responsible for DNA binding. Mutations in this region result in sex reversal, where the opposite sex is produced.^[8] Because there is little conservation, the SRY promoter, regulatory elements and regulation are not well understood. Within related mammalian groups there are homologies within the first 400-600 base pairs upstream from the translational start site. In vitro studies of human SRY promoter have shown that a region of at least 310 bp upstream to translational start site are required for SRY promoter function. It's been shown that binding of three transcription factors, Steroidogenic factor 1 (SF1), Specificity Protein 1 (Sp1 transcription factor) and Wilms tumor protein 1 (WT1), to the human promoter sequence, influence expression of SRY.^[8]

The promoter region has two Sp1 binding sites, at -150 and -13 that function as regulatory sites. Sp1 is a transcription factor that binds GC-rich consensus sequences, and mutation of the SRY binding sites leads to a 90% reduction in gene transcription. Studies of SF1 have resulted in less definite results . Mutations of SF1 can lead to sex reversal and deletion lead to incomplete gonad development. However, it's not clear how SF1 interacts with the SR1 promoter directly.^[9] The promoter region also has two WT1 binding sites at -78 and -87 bp from the ATG codon. WT1 is transcription factor that has four C-terminal Zinc fingers and an N-terminal Pro/Glu-rich region and primarily functions as an activator. Mutation of the Zinc fingers or inactivation of WT1 results in reduced male gonad size. Deletion of the gene resulted in complete sex reversal. It is not clear how WT1 functions to up-regulate SRY, but some research suggests that it helps stabilize message processing.^[9] However, there are complications to this hypothesis, because WT1 also is responsible for expression of an antagonist of male development, DAX1, which stands for Dosage-sensitive sex reversal, Adrenal hypoplasia critical region, on chromosome X, gene 1 . An additional copy of DAX1 in mice leads to sex reversal. It is not clear how DAX1 functions, and many different pathways have been suggested, including SRY transcriptional destabilization and RNA binding. There is evidence from work on suppression of male development that DAX1 can interfere with function of SF1, and in turn transcription of SRY by recruiting corepressors.^[8]

There is also evidence that GATA binding protein 4 (GATA4) and FOG2 contribute to activation of SRY by associating with its promoter. How these proteins regulate SRY transcription is not clear, but FOG2 and GATA4 mutants have significantly lower levels of SRY transcription.^[10] FOGs have zinc finger motifs that can bind DNA, but there is no evidence of FOG2 interaction with SRY. Studies suggest that FOG2 and GATA4 associate with nucleosome remodeling proteins that could lead to its activation.^[11]

Function

During gestation, the cells of the primordial gonad that lie along the urogenital ridge are in a bipotential state, meaning they possess the ability to become either male cells (Sertoli and Leydig cells) or female cells (follicle cells and Theca cells). TDF initiates testis differentiation by activating male-specific transcription factors that allow these bipotential cells to differentiate and proliferate. TDF accomplishes this by upregulating SOX9, a transcription factor with a DNA-binding site very similar to TDF's. SOX9 leads to the upregulation of fibroblast growth factor 9 (Fgf9), which in turn leads to further upregulation of SOX9 . Once proper SOX9 levels are reached, the bipotential cells of the gonad begin to differentiate into Sertoli cells. Additionally, cells expressing TDF will continue to proliferate to form the primordial testis. While this constitutes the basic series of events, this brief review should be taken with caution since there are many more factors that influence sex differentiation.

Action in the nucleus

The TDF protein consists of three main regions. The central region encompasses the HMG (high-motility group) domain, which contains nuclear localization sequences and acts as the DNA-binding domain. The C-terminal domain has no conserved structure, and the N-terminal domain can be phosphorylated to enhance DNA-binding.^[9] The process begins with nuclear localization of TDF by acetylation of the nuclear localization signal regions, which allows for the binding of importin β and calmodulin to TDF, facilitating its import into the nucleus. Once in the nucleus, TDF and SF1 (steroidogenic factor 1, another transcriptional regulator) complex and bind to TESCO (testis-specific enhancer of Sox9 core), the testes-specific enhancer element of the Sox9 gene in Sertoli cell precursors, located upstream of the Sox9 gene transcription start site.^[3] Specifically, it is the HMG region of TDF that binds to the minor groove of the DNA target sequence, causing the DNA to bend and unwind. The establishment of this particular DNA “architecture” facilitates the transcription of the Sox9 gene.^[9] SOX9 protein then initiates a positive feedback loop, involving SOX9 acting as its own transcription factor and resulting in the synthesis of large amounts of SOX9.^[9]

SOX9 and testes differentiation

The SF1 protein, on its own, leads to minimal transcription of the SOX9 gene in both the XX and XY bipotential gonadal cells along the urogenital ridge. However, binding of the TDF-SF1 complex to the testis-specific enhancer (TESCO) on SOX9 leads to significant up-regulation of the gene in only the XY gonad, while transcription in the XX gonad remains negligible. Part of this up-regulation is accomplished by SOX9 itself through a positive feedback loop; like TDF, SOX9 complexes with SF1 and binds to the TESCO enhancer, leading to further expression of SOX9 in the XY gonad. Two other proteins, FGF9 (fibroblast growth factor 9) and PDG2 (prostaglandin D2), also maintain this up-regulation. Although their exact pathways are not fully understood, they have been proven to be essential for the continued expression of SOX9 at the levels necessary for testes development.^[3]

SOX9 and TDF are believed to be responsible for the cell-autonomous differentiation of supporting cell precursors in the gonads into Sertoli cells, the beginning of testes development. These initial Sertoli cells, in the center of the gonad, are hypothesized to be the starting point for a wave of FGF9 that spreads throughout the developing XY gonad, leading to further differentiation of Sertoli cells via the up-regulation of SOX9.^[12] SOX9 and TDF are also believed to be responsible for many of the later processes of testis development (such as Leydig cell differentiation, sex cord formation, and formation of testis-specific vasculature), although exact mechanisms remain unclear.^[13] It has been shown, however, that SOX9, in the presence of PDG2, acts directly on Amh (encoding anti-Müllerian hormone) and is capable of inducing testis formation in XX mice gonads, indicating its vital to testes development.^[12]

Influence on sex

Embryos are gonadally identical, regardless of genetic sex, until a certain point in development when the testis-determining factor causes male sex organs to develop. Therefore, SRY plays an important role in sex determination. A typical male karyotype is XY. Individuals who inherit a normal Y chromosome and multiple X chromosomes are generally male (such as in Klinefelter Syndrome, which has an XXY karyotype). A genetic recombination event known as crossing over can result in karyotypes that do not match their phenotypic expression.

Crossing over during paternal meiosis prior to conception can cause SRY to be transferred from the Y chromosome to the X chromosome. The Y chromosome that results from this crossover is now lacking an SRY gene, and can no longer initiate testis development. When this chromosome is inherited from the father, the resulting offspring will have Swyer syndrome, characterized by a male karyotype (XY) and a female phenotype. The X chromosome that results from this crossover event now has a SRY gene, and therefore the ability to initiate testis development. Offspring who inherit this chromosome will have a condition called XX male syndrome, characterized by an XX karyotype, and a male phenotype. While most XX males develop phenotypically as males, is it possible for them to experience incomplete differentiation of the testis, resulting in the formation of both testicular and ovarian in the same individual. This true sterile hermaphroditism (not to be confused with the hermaphroditism of hermaphroditic species and taxa such as earthworms, as they can reproduce) is most likely caused by the inactivation (either random or non-random) of the X chromosome containing the SRY in some cells.^[14]

While the presence or absence of SRY has generally determined whether or not testis development occurs, it has been suggested that there are other factors that affect the functionality of SRY.^[15] Therefore, there are individuals who have the SRY gene, but still develop as females, either because the gene itself is defective or mutated, or because one of the contributing factors is defective.^[16] This can happen in individuals exhibiting a XY, XXY, or XX SRY-positive karyotype.

Role in other diseases

SRY has been shown to interact with the androgen receptor and individuals with XY karyotype and a functional SRY gene can have an outwardly female phenotype due to an underlying androgen insensitivity syndrome (AIS).^[17] Individuals with AIS are unable to respond to androgens properly due to a defect in their androgen receptor gene, and affected individuals can have complete or partial AIS.^[18] SRY has also been linked to the fact that males are more likely than females to develop dopamine-related diseases such as schizophrenia and Parkinson's disease. SRY encodes a protein that controls the concentration of dopamine, the neurotransmitter that carries signals from the brain that control movement and coordination.^[19]

Use in Olympic screening

One of the most controversial uses of this discovery was as a means for gender verification at the Olympic Games, under a system implemented by the International Olympic Committee in 1992. Athletes with an SRY gene were not permitted to participate as females, although all athletes in whom this was "detected" at the 1996 Summer Olympics were ruled false positives and were not disqualified. Specifically, eight female participants (out of a total of 3387) at these games were found to have the SRY gene. However, after further investigation of their genetic conditions, all these athletes were verified as female and allowed to compete. These athletes were found to have either partial or full androgen insensitivity, despite having an SRY gene, making them phenotypically female and giving them no advantage over other female competitors.^[20] In the late 1990s, a number of relevant professional societies in United States called for elimination of gender verification, including the American Medical Association, stating that the method used was uncertain and ineffective.^[21] The screening was eliminated as of the 2000 Summer Olympics.^[21]^[22]^[23] Since this method of testing was eliminated there has been no form of Olympic gender screening that all athletes must undergo. Rather, questions regarding an athlete's gender are now addressed on an individual basis by medical experts, only when there is significant reason to suspect a male athlete may be posing as a female. However, there have been few, if any, instances of such suspicion and evaluation since the system of screening was eliminated, due to the difficulties and impracticality of a male successfully disguising himself as a female athlete (such as the nature of women's event uniforms, which make concealment of a male's body near impossible).^[20]

Ongoing research

Despite the progress made during the past several decades in the study of sex determination, the SRY gene, and the TDF protein, work is still being done to further our understanding in these areas. There remain factors that need to be identified in the sex-determining molecular network, and the chromosomal changes involved in many other human sex-reversal cases are still unknown. Scientists continue to search for additional sex-determining genes, using techniques such as microarray screening of the genital ridge genes at varying developmental stages, mutagenesis screens in mice for sex-reversal phenotypes, and identifying the genes that transcription factors act on using chromatin immunoprecipitation.^[9]

References

^ Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M (November 1990). "Genetic evidence equating SRY and the testis-determining factor". Nature 348 (6300): 448–50. Bibcode:1990Natur.348..448B. doi:10.1038/348448A0. PMID 2247149.
^ Wallis MC, Waters PD, Graves JA (June 2008). "Sex determination in mammals - Before and after the evolution of SRY". Cell. Mol. Life Sci. 65 (20): 3182–95. doi:10.1007/s00018-008-8109-z. PMID 18581056.
^ ^a ^b ^c Kashimada K, Koopman P (December 2010). "Sry: the master switch in mammalian sex determination". Development 137 (23): 3921–30. doi:10.1242/dev.048983. PMID 21062860.
^ Mittwoch U (October 1988). "The race to be male". New Scientist 120 (1635): 38–42.
^ Katoh K, Miyata T (1999). "A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY". FEBS Lett 463 (1–2): 129–32. doi:10.1016/S0014-5793(99)01621-X. PMID 10601652.
^ Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA (June 2008). "Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes". Genome Res. 18 (6): 965–73. doi:10.1101/gr.7101908. PMC 2413164. PMID 18463302.
^ Bowles J, Schepers G, Koopman P (2000). "Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators". Dev Biol 227 (2): 239–55. doi:10.1006/dbio.2000.9883. PMID 11071752.
^ ^a ^b ^c Ely D, Underwood A, Dunphy G, Boehme S, Turner M, Milsted A (November 2010). "Review of the Y chromosome, Sry and hypertension". Steroids 75 (11): 747–53. doi:10.1016/j.steroids.2009.10.015. PMC 2891862. PMID 19914267.
^ ^a ^b ^c ^d ^e ^f Harley VR, Clarkson MJ, Argentaro A (August 2003). "The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]". Endocr. Rev. 24 (4): 466–87. doi:10.1210/er.2002-0025. PMID 12920151.
^ Knower KC, Kelly S, Harley VR (2003). "Turning on the male--SRY, SOX9 and sex determination in mammals". Cytogenet. Genome Res. 101 (3-4): 185–98. doi:10.1159/000074336. PMID 14684982.
^ Friedman, Theodore (2011). Advances in Genetics Vol 76. 108: Elsevier Inc.
^ ^a ^b McClelland K, Bowles J, Koopman P (January 2012). "Male sex determination: insights into molecular mechanisms". Asian J. Androl. 14 (1): 164–71. doi:10.1038/aja.2011.169. PMC 3735148. PMID 22179516.
^ Sekido R, Lovell-Badge R (2013). "Genetic control of testis development". Sex Dev 7 (1–3): 21–32. doi:10.1159/000342221. PMID 22964823.
^ Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F (January 2000). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". Am. J. Med. Genet. 90 (1): 25–8. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5. PMID 10602113.
^ Polanco JC, Koopman P (February 2007). "Sry and the hesitant beginnings of male development". Dev. Biol. 302 (1): 13–24. doi:10.1016/j.ydbio.2006.08.049. PMID 16996051.
^ Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ (May 2009). "Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene". Am. J. Hum. Genet. 84 (5): 658–63. doi:10.1016/j.ajhg.2009.03.016. PMC 2680992. PMID 19361780.
^ Yuan X, Lu ML, Li T, Balk SP (December 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". J. Biol. Chem. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838.
^ Lister Hill National Center for Biomedical Communications (2008). "Androgen insensitivity syndrome". Genetics Home Reference. U.S. National Library of Medicine.
^ Dewing P, Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (February 2006). "Direct regulation of adult brain function by the male-specific factor SRY". Curr. Biol. 16 (4): 415–20. doi:10.1016/j.cub.2006.01.017. PMID 16488877.
^ ^a ^b "Olympic Gender Testing".
^ ^a ^b Facius GM (2004-08-01). "The Major Medical Blunder of the 20th Century". Gender Testing. facius-homepage.dk. Retrieved 2011-06-12. ^{[dead link]}
^ Elsas LJ, Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). "Gender verification of female athletes". Genet. Med. 2 (4): 249–54. doi:10.1097/00125817-200007000-00008. PMID 11252710.
^ Dickinson BD, Genel M, Robinowitz CB, Turner PL, Woods GL (October 2002). "Gender verification of female Olympic athletes". Med Sci Sports Exerc 34 (10): 1539–42; discussion 1543. doi:10.1097/00005768-200210000-00001. PMID 12370551.

External links

GeneReviews/NCBI/NIH/UW entry on 46,XX Testicular Disorder of Sex Development
OMIM entries on 46,XX Testicular Disorder of Sex Development
Genes, sry at the US National Library of Medicine Medical Subject Headings (MeSH)
Sex-Determining Region Y Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 外陰部異常を有する幼児の評価 evaluation of the infant with ambiguous genitalia
2. 正常な性的発育 normal sexual development
3. 性染色体異常 sex chromosome abnormalities
4. Etiology and pathogenesis of Parkinson disease
5. Lambert-Eaton筋無力症候群の治療 treatment of lambert eaton myasthenic syndrome

English Journal

Targeted gene expression profiling in European sea bass (Dicentrarchus labrax, L.) follicles from primary growth to late vitellogenesis.

Garcia-Lopez A, Sanchez-Amaya MI, Prat F.AbstractA real-time PCR-based gene expression survey was performed on isolated European sea bass follicles from primary growth to late vitellogenesis. Expression levels of 18 transcripts with demonstrated relevance during oogenesis, encoding gonadotropin, thyrotropin, estrogen, androgen, and vitellogenin receptors, steroidogenesis-related as well as growth and transcription factors were measured. Primary oocytes showed high mRNA levels of insulin-like growth factors 1 and 2, bone morphogenetic protein 4, estrogen receptor 2b, androgen receptor b, and SRY-box containing gene 17 together with low transcript amounts of gonadotropin receptors. Follicles at the lipid vesicles stage (i.e., the beginning of the secondary growth phase) showed elevated mRNA amounts of follicle stimulating hormone receptor (fshr) and anti-Mullerian hormone. Early-to-mid vitellogenic follicles showed high mRNA levels of fshr and cytochrome P450, family 19, subfamily A, polypeptide 1a while mid-to-late vitellogenic follicles expressed increasing transcript amounts of luteinizing hormone/choriogonadotropin receptor, steroidogenic acute regulatory protein, and estrogen receptors 1 and 2a. The molecular data presented here may serve as a solid base for future studies focused on unraveling the specific mechanisms orchestrating follicular development in teleost fish.
Comparative biochemistry and physiology. Part A, Molecular & integrative physiology.Comp Biochem Physiol A Mol Integr Physiol.2011 Nov;160(3):374-80. Epub 2011 Jul 12.
A real-time PCR-based gene expression survey was performed on isolated European sea bass follicles from primary growth to late vitellogenesis. Expression levels of 18 transcripts with demonstrated relevance during oogenesis, encoding gonadotropin, thyrotropin, estrogen, androgen, and vitellogenin re
PMID 21782032

Novel homozygous mutations in Desert Hedgehog gene in patients with 46,XY complete gonadal dysgenesis and prediction of its structural and functional implications by computational methods.

Das DK, Sanghavi D, Gawde H, Idicula-Thomas S, Vasudevan L.SourceGenetic Research Centre, National Institute for Research in Reproductive Health (ICMR), Jahangir Merwanji Street, Parel, Mumbai 400 012, India.
European journal of medical genetics.Eur J Med Genet.2011 November - December;54(6):e529-e534. Epub 2011 Jul 23.
Male to female sex reversal in patients with 46,XY karyotype results from the failure of development of testis which may be due to mutations in the SRY gene. Only 10-15% of cases of 46,XY gonadal dysgenesis are accounted for by different types of mutations in the SRY gene. Hence, majority of such pa
PMID 21816240

Japanese Journal

A New Method for Sex Determination Based on Detection of SRY, STS and Amelogenin Gene Regions with Simultaneous Amplification of Their Homologous Sequences by a Multiplex PCR

Morikawa Toshio,Yamamoto Yuji,Miyaishi Satoru
Acta Medica Okayama 65(2), 113-122, 2011-04
… We have developed a new method for sex determination based on simultaneous detection of the SRY (sex-determining region Y), STS (steroid sulfatase) and amelogenin (AMELX and AMELY) gene regions and their homologous sequences. …
NAID 120002970768

Phylogeographic sympatry and isolation of the Eurasian badgers (Meles, Mustelidae, Carnivora): implications for an alternative analysis using maternally as well as paternally inherited genes

Tashima Sara,Kaneko Yayoi,Anezaki Tomoko [他]
Zoological science 28(4), 293-303, 2011-04
NAID 40018787462

Related Pictures

★リンクテーブル★

リンク元	「外性器」「性決定領域Y」「性決定遺伝子Y」
拡張検索	「SRY遺伝子」
関連記事	「SR」「S」

「外性器」

Sex determining region Y
	; PDB rendering based on 1hry.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1HRY, 1HRZ, 1J46, 1J47, 2GZK
Identifiers
Symbols	SRY ; SRXX1; SRXY1; TDF; TDY
External IDs	OMIM: 480000 MGI: 98660 HomoloGene: 48168 GeneCards: SRY Gene
Gene ontology
Molecular function	• DNA binding; • RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; • calmodulin binding; • transcription factor binding;
Cellular component	• nucleus; • cytoplasm; • nuclear speck;
Biological process	• regulation of transcription from RNA polymerase II promoter; • transcription from RNA polymerase II promoter; • sex differentiation; • cell differentiation; • male sex determination; • positive regulation of transcription, DNA-templated; • positive regulation of male gonad development;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: external genitalia, edea
関: 外陰部
同: 外生殖器

[show details]

外性器 : 約 161,000 件
外生殖器 : 約 3,800 件

発生(みえ9.47)

		女性	男性
生殖結節		陰核	陰茎
排泄腔膜	尿生殖膜	膣前庭	(閉鎖)
排泄腔膜	肛門膜
排泄腔ヒダ	尿道ヒダ	小陰唇	包皮
排泄腔ヒダ	肛門ヒダ
生殖隆起		大陰唇	陰嚢

カウパー腺　⇔　バルトリン腺

外性器の性の決定

Y染色体、このなかでもSRY遺伝子が性の決定に関わっている？？？？？

「性決定領域Y」

　　[★]

英: sex-determining region Y SRY
関: 性決定遺伝子Y

「性決定遺伝子Y」

　　[★]

英: sex-determining gene Y
同: SRY

「SRY遺伝子」

　　[★]

英: SRY gene
同: 性決定遺伝子 sex determining gene、精巣決定遺伝子 TDF gene testis-determining factor gene
関: 性染色体、精巣決定遺伝子群

「SR」

　　[★]

筋小胞体 sarcoplasmic reticula sarcoplasmic reticulum

「S」

　　[★]

[1] 

遺伝子記号およびタンパク質記号の表記は、生物種ごとに異なっている（右の付表および遺伝子命名法を参照）。この記事では明らかにラット・マウスの遺伝子である場合を除いて、哺乳類Sex-determining region Y遺伝子のオーソログ全てをSRYで統一して表記する。
付表．Sex-determining region Y 遺伝子とタンパク質の表記
種遺伝子記号タンパク質記号

ヒト Homo sapiens SRY SRY

ラット Mus musculus
マウス Rattus norvegicus Sry SRY

[muto-2] 武藤照子「哺乳類における性決定遺伝子と生殖巣の分化」（岡田益吉、長濱嘉孝、中辻憲夫編『生殖細胞の発生と性分化』）

[morohashi-3] 諸橋憲一「哺乳類における生殖腺の性分化」『蛋白質核酸酵素』2004年2月号

[4] Yoshimoto S, Okada E, Umemoto H, Tamura K, Uno Y, Nishida-Umehara C, Matsuda Y, Takamatsu N, Shiba T, Ito M (2008). “A W-linked DM-domain gene, DM-W, participates in primary ovary development in Xenopus laevis”. Proc Natl Acad Sci USA 105: 2469-2474. doi:10.1073/pnas.0712244105 2009年5月2日閲覧。.

[matsuda-5] Matsuda M, Nagahama Y, Shinomiya A, Sato T, Matsuda C, Kobayashi T, Morrey CE, Shibata N, Asakawa S, Shimizu N, Hori H, Hamaguchi S, Sakaizumi M (2002). “DMY is a Y-specific DM-domain gene required for male development in the medaka fish”. Nature 417: 559-563. doi:10.1038/nature751. PMID 12037570.

[nagai-6] 長井光三「哺乳動物における性決定の分子機構」『蛋白質核酸酵素』1994年8月号

[biol_sds-7] 八杉竜一ら編「性決定物質」『岩波生物学辞典（第4版）』

[biol_tdf-8] 八杉竜一ら編「精巣決定因子」『岩波生物学辞典（第4版）』

[sinclair-9] Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf AM, Lovell-Badge R, Goodfellow PN (1990). “A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif”. Nature 346: 216-217. doi:doi:10.1038/346240a0. PMID 1695712.

[10] SRY遺伝子が発現すると雄に分化するため、厳密に言うとSRYは限性遺伝の原因となる遺伝子である。

[kuroiwa-11] 黒岩麻里「Y染色体を失った哺乳類，トゲネズミ」『生物の科学遺伝』2009年1月号

[bainbridge_1-12] デイヴィッド・ベインブリッジ『X染色体：男と女を決めるもの』79-83ページ

[13] Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA (2008). “Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes”. Genome Res 18: 965-973. doi:10.1101/gr.7101908 2009年5月24日閲覧。.

[koopman-14] Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991). “Male development of chromosomally female mice transgenic for SRY”. Nature 351: 117-121. doi:10.1038/351117a0. PMID 2030730.

[entres-15] "Entrez Gene: SRY sex determining region Y" 2009年6月3日閲覧。

[16] Dewing P, Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (2006). “Direct regulation of adult brain function by the male-specific factor SRY”. Curr Biol 16: 415-420. PMID 16488877.

[17] アメリカ合衆国・国立生物工学情報センター（NCBI） - HomoloGene

[morohashi_2-18] 諸橋憲一「哺乳類生殖巣の分化」（岡田益吉、長濱嘉孝、中辻憲夫編『生殖細胞の発生と性分化』）

[19] SOXファミリーの一部は性分化に強く関与しているものと考えられているが、その機能は哺乳類と他の生物では異なる場合もある。たとえばSOX9は哺乳類の生殖腺形成に関与しているが、鳥類では発現時期が異なるため異なる作用を持つと考えられている（諸橋憲一「哺乳類における生殖腺の性分化」『蛋白質核酸酵素』）

[20] 八杉竜一ほか編「性染色質」「Yクロマチン」『岩波生物学辞典』

[elasas-21] Elsas, LJ; Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). “Gender verification of female athletes”. Genetics in Medicine 2 (4): 249–254. PMID 11252710.

[22] Dickinson, BD; Genel M, Robinowitz CB, Turner PL, Woods GL (2002). “Gender verification of female Olympic athletes”. Medicine & Science in Sports & Exercise 34 (10): 1543. PMID 12370551.

[TDF-1] Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M (November 1990). "Genetic evidence equating SRY and the testis-determining factor". Nature 348 (6300): 448–50. Bibcode:1990Natur.348..448B. doi:10.1038/348448A0. PMID 2247149.

[pmid18581056-2] Wallis MC, Waters PD, Graves JA (June 2008). "Sex determination in mammals - Before and after the evolution of SRY". Cell. Mol. Life Sci. 65 (20): 3182–95. doi:10.1007/s00018-008-8109-z. PMID 18581056.

[Kashimada_Koopman_2010-3] Kashimada K, Koopman P (December 2010). "Sry: the master switch in mammalian sex determination". Development 137 (23): 3921–30. doi:10.1242/dev.048983. PMID 21062860.

[Mittwoch_1988-4] Mittwoch U (October 1988). "The race to be male". New Scientist 120 (1635): 38–42.

[5] Katoh K, Miyata T (1999). "A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY". FEBS Lett 463 (1–2): 129–32. doi:10.1016/S0014-5793(99)01621-X. PMID 10601652.

[pmid18463302-6] Veyrunes F, Waters PD, Miethke P, Rens W, McMillan D, Alsop AE, Grützner F, Deakin JE, Whittington CM, Schatzkamer K, Kremitzki CL, Graves T, Ferguson-Smith MA, Warren W, Marshall Graves JA (June 2008). "Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes". Genome Res. 18 (6): 965–73. doi:10.1101/gr.7101908. PMC 2413164. PMID 18463302.

[7] Bowles J, Schepers G, Koopman P (2000). "Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators". Dev Biol 227 (2): 239–55. doi:10.1006/dbio.2000.9883. PMID 11071752.

[pmid19914267-8] Ely D, Underwood A, Dunphy G, Boehme S, Turner M, Milsted A (November 2010). "Review of the Y chromosome, Sry and hypertension". Steroids 75 (11): 747–53. doi:10.1016/j.steroids.2009.10.015. PMC 2891862. PMID 19914267.

[Harley_2003-9] ^ ^a ^b ^c ^d ^e ^f Harley VR, Clarkson MJ, Argentaro A (August 2003). "The molecular action and regulation of the testis-determining factors, SRY (sex-determining region on the Y chromosome) and SOX9 [SRY-related high-mobility group (HMG) box 9]". Endocr. Rev. 24 (4): 466–87. doi:10.1210/er.2002-0025. PMID 12920151.

[pmid14684982-10] Knower KC, Kelly S, Harley VR (2003). "Turning on the male--SRY, SOX9 and sex determination in mammals". Cytogenet. Genome Res. 101 (3-4): 185–98. doi:10.1159/000074336. PMID 14684982.

[11] Friedman, Theodore (2011). Advances in Genetics Vol 76. 108: Elsevier Inc.

[pmid22179516-12] McClelland K, Bowles J, Koopman P (January 2012). "Male sex determination: insights into molecular mechanisms". Asian J. Androl. 14 (1): 164–71. doi:10.1038/aja.2011.169. PMC 3735148. PMID 22179516.

[pmid22964823-13] Sekido R, Lovell-Badge R (2013). "Genetic control of testis development". Sex Dev 7 (1–3): 21–32. doi:10.1159/000342221. PMID 22964823.

[pmid10602113-14] Margarit E, Coll MD, Oliva R, Gómez D, Soler A, Ballesta F (January 2000). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". Am. J. Med. Genet. 90 (1): 25–8. doi:10.1002/(SICI)1096-8628(20000103)90:1<25::AID-AJMG5>3.0.CO;2-5. PMID 10602113.

[pmid16996051-15] Polanco JC, Koopman P (February 2007). "Sry and the hesitant beginnings of male development". Dev. Biol. 302 (1): 13–24. doi:10.1016/j.ydbio.2006.08.049. PMID 16996051.

[pmid19361780-16] Biason-Lauber A, Konrad D, Meyer M, DeBeaufort C, Schoenle EJ (May 2009). "Ovaries and female phenotype in a girl with 46,XY karyotype and mutations in the CBX2 gene". Am. J. Hum. Genet. 84 (5): 658–63. doi:10.1016/j.ajhg.2009.03.016. PMC 2680992. PMID 19361780.

[pmid11585838-17] Yuan X, Lu ML, Li T, Balk SP (December 2001). "SRY interacts with and negatively regulates androgen receptor transcriptional activity". J. Biol. Chem. 276 (49): 46647–54. doi:10.1074/jbc.M108404200. PMID 11585838.

[url_Androgen_insensitivity_syndrome_-_Genetics_Home_Reference-18] Lister Hill National Center for Biomedical Communications (2008). "Androgen insensitivity syndrome". Genetics Home Reference. U.S. National Library of Medicine.

[pmid16488877-19] Dewing P, Chiang CW, Sinchak K, Sim H, Fernagut PO, Kelly S, Chesselet MF, Micevych PE, Albrecht KH, Harley VR, Vilain E (February 2006). "Direct regulation of adult brain function by the male-specific factor SRY". Curr. Biol. 16 (4): 415–20. doi:10.1016/j.cub.2006.01.017. PMID 16488877.

[Olympic_Gender_Testing-20] "Olympic Gender Testing".

[url_Facius-21] Facius GM (2004-08-01). "The Major Medical Blunder of the 20th Century". Gender Testing. facius-homepage.dk. Retrieved 2011-06-12. ^{[dead link]}

[pmid11252710-22] Elsas LJ, Ljungqvist A, Ferguson-Smith MA, Simpson JL, Genel M, Carlson AS, Ferris E, de la Chapelle A, Ehrhardt AA (2000). "Gender verification of female athletes". Genet. Med. 2 (4): 249–54. doi:10.1097/00125817-200007000-00008. PMID 11252710.

[pmid12370551-23] Dickinson BD, Genel M, Robinowitz CB, Turner PL, Woods GL (October 2002). "Gender verification of female Olympic athletes". Med Sci Sports Exerc 34 (10): 1539–42; discussion 1543. doi:10.1097/00005768-200210000-00001. PMID 12370551.

匿名

検索

案内

SRY