Genomes and Genes
Gene Symbol: Amh
Description: anti-Mullerian hormone
Alias: MIS, muellerian-inhibiting factor, Mullerian inhibiting substance, anti-Muellerian hormone, muellerian-inhibiting substance
- Sutton E, Hughes J, White S, Sekido R, Tan J, Arboleda V, et al. Identification of SOX3 as an XX male sex reversal gene in mice and humans. J Clin Invest. 2011;121:328-41 pubmed publisher..Together, these data suggest that SOX3 and SRY are functionally interchangeable in sex determination and support the notion that SRY evolved from SOX3 via a regulatory mutation that led to its de novo expression in the early gonad. ..
- Hammes A, Guo J, Lutsch G, Leheste J, Landrock D, Ziegler U, et al. Two splice variants of the Wilms' tumor 1 gene have distinct functions during sex determination and nephron formation. Cell. 2001;106:319-29 pubmed..Our data demonstrate distinct functions for the two splice variants and place the +KTS variants as important regulators for Sry in the sex determination pathway. ..
- Schmidt D, Ovitt C, Anlag K, Fehsenfeld S, Gredsted L, Treier A, et al. The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance. Development. 2004;131:933-42 pubmed..In addition to providing a molecular mechanism for premature ovarian failure in BPES, these results suggest that granulosa cell function is not only crucial for oocyte growth but also to maintain follicular quiescence in vivo. ..
- Lavery R, Lardenois A, Ranc Jianmotamedi F, Pauper E, Gregoire E, Vigier C, et al. XY Sox9 embryonic loss-of-function mouse mutants show complete sex reversal and produce partially fertile XY oocytes. Dev Biol. 2011;354:111-22 pubmed publisher..Taken together, we found that XY Sf1:Cre(Tg/+); Sox9(flox/flox) females are capable of producing viable offspring albeit at a reduced level. ..
- Polanco J, Wilhelm D, Davidson T, Knight D, Koopman P. Sox10 gain-of-function causes XX sex reversal in mice: implications for human 22q-linked disorders of sex development. Hum Mol Genet. 2010;19:506-16 pubmed publisher..1, our results functionally implicate SOX10 in the etiology of these DSDs. ..
- Arango N, Lovell Badge R, Behringer R. Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. Cell. 1999;99:409-19 pubmed..into conserved steroidogenic factor 1 (SF1)- and SOX9-binding sites within the endogenous mouse Mullerian inhibiting substance (Mis) promoter...
- Munsterberg A, Lovell Badge R. Expression of the mouse anti-müllerian hormone gene suggests a role in both male and female sexual differentiation. Development. 1991;113:613-24 pubmed..to the mouse gene encoding anti-Müllerian hormone, and the use of these clones as molecular probes to study AMH gene expression. We constructed a 14...
- Racine C, Rey R, Forest M, Louis F, Ferre A, Huhtaniemi I, et al. Receptors for anti-müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Proc Natl Acad Sci U S A. 1998;95:594-9 pubmedStrong overexpression of anti-Müllerian hormone (AMH) in transgenic mice leads to incomplete fetal virilization and decreased serum testosterone in the adult. Conversely, AMH-deficient mice exhibit Leydig cell hyperplasia...
- Jameson S, Lin Y, Capel B. Testis development requires the repression of Wnt4 by Fgf signaling. Dev Biol. 2012;370:24-32 pubmed publisher..However, we found that the relationship between these two signaling factors is not symmetric: loss of Fgf9 in XX Wnt4(-/-) gonads does not rescue their partial female-to-male sex-reversal. ..
- Moniot B, Declosmenil F, Barrionuevo F, Scherer G, Aritake K, Malki S, et al. The PGD2 pathway, independently of FGF9, amplifies SOX9 activity in Sertoli cells during male sexual differentiation. Development. 2009;136:1813-21 pubmed publisher..This mechanism participates together with FGF9 as an amplification system of Sox9 gene expression and activity during mammalian testicular organogenesis. ..
- Barsoum I, Bingham N, Parker K, Jorgensen J, Yao H. Activation of the Hedgehog pathway in the mouse fetal ovary leads to ectopic appearance of fetal Leydig cells and female pseudohermaphroditism. Dev Biol. 2009;329:96-103 pubmed publisher..This study provides not only insights into mechanisms of cell lineage specification in gonads, but also a model to understand defects in sexual differentiation. ..
- Vidal V, Chaboissier M, de Rooij D, Schedl A. Sox9 induces testis development in XX transgenic mice. Nat Genet. 2001;28:216-7 pubmed..Here, we show that Sox9 is sufficient to induce testis formation in mice, indicating that it can substitute for the sex-determining gene Sry. ..
- Barrionuevo F, Georg I, Scherthan H, Lecureuil C, Guillou F, Wegner M, et al. Testis cord differentiation after the sex determination stage is independent of Sox9 but fails in the combined absence of Sox9 and Sox8. Dev Biol. 2009;327:301-12 pubmed publisher..is required for testis development after the initial steps of sex determination, we crossed Sox9(flox) mice with an AMH-Cre transgenic line thereby completely deleting Sox9 in Sertoli cells by E14.0...
- Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, Chaboissier M, et al. Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol. 2006;4:e187 pubmed..In principle, sex determination in other vertebrates may operate through any switch that introduces an imbalance between these two signaling pathways. ..
- Bouma G, Washburn L, Albrecht K, Eicher E. Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice. Proc Natl Acad Sci U S A. 2007;104:14994-9 pubmed..We propose that in humans the FOG2 and/or GATA4 genes might be haploinsufficient for normal testis determination and thus could be the cause of some previously unassigned cases of XY gonadal sex reversal. ..
- Moniot B, Farhat A, Aritake K, Declosmenil F, Nef S, Eguchi N, et al. Hematopoietic prostaglandin D synthase (H-Pgds) is expressed in the early embryonic gonad and participates to the initial nuclear translocation of the SOX9 protein. Dev Dyn. 2011;240:2335-43 pubmed publisher..5 early stage of mouse testicular differentiation suggesting a role for H-Pgds-produced PGD(2) in the initial nuclear translocation of SOX9. ..
- Vainio S, Heikkilä M, Kispert A, Chin N, McMahon A. Female development in mammals is regulated by Wnt-4 signalling. Nature. 1999;397:405-9 pubmed..b>Mullerian inhibiting substance and testosterone secreted by the differentiating embryonic testes result in the loss of female (..
- Lee C, Taketo T. Normal onset, but prolonged expression, of Sry gene in the B6.YDOM sex-reversed mouse gonad. Dev Biol. 1994;165:442-52 pubmed..YDOM gonad appears to be impaired downstream of Sry transcription, resulting in persistent Sry transcripts and a delay in onset of other genes involved in testicular differentiation. ..
- Barrionuevo F, Bagheri Fam S, Klattig J, Kist R, Taketo M, Englert C, et al. Homozygous inactivation of Sox9 causes complete XY sex reversal in mice. Biol Reprod. 2006;74:195-201 pubmed..Our results provide in vivo proof that, in contrast to the situation in humans, complete XY sex reversal in mice requires inactivation of both Sox9 alleles and that Sox9 is essential for testogenesis in mice. ..
- Jamin S, Arango N, Mishina Y, Hanks M, Behringer R. Requirement of Bmpr1a for Müllerian duct regression during male sexual development. Nat Genet. 2002;32:408-10 pubmed..the fetal testis produces the transforming growth factor beta (TGF-beta) family member anti-Müllerian hormone (Amh, also known as Müllerian-inhibiting substance (Mis)), which causes regression of the Müllerian ducts, the ..
- Maatouk D, DiNapoli L, Alvers A, Parker K, Taketo M, Capel B. Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet. 2008;17:2949-55 pubmed publisher..The identification of beta-catenin as a key pro-ovarian and anti-testis signaling molecule will further our understanding of the mechanisms controlling sex determination and the molecular mechanisms that lead to sex-reversal. ..
- Nef S, Verma Kurvari S, Merenmies J, Vassalli J, Efstratiadis A, Accili D, et al. Testis determination requires insulin receptor family function in mice. Nature. 2003;426:291-5 pubmed..Reduced expression of both Sry and the early testis-specific marker Sox9 indicates that the insulin signalling pathway is required for male sex determination. ..
- Gregoire E, Lavery R, Chassot A, Akiyama H, Treier M, Behringer R, et al. Transient development of ovotestes in XX Sox9 transgenic mice. Dev Biol. 2011;349:65-77 pubmed publisher..Finally, ovarian cells of the XX Wt1:Sox9 ovotestis undergo apoptosis during late embryogenesis leading to complete female-to-male sex reversal of the transgenic mice at birth...
- Katoh Fukui Y, Miyabayashi K, Komatsu T, Owaki A, Baba T, Shima Y, et al. Cbx2, a polycomb group gene, is required for Sry gene expression in mice. Endocrinology. 2012;153:913-24 pubmed publisher..However, testes remained hypoplastic in these mice, indicating that the size and the sex of the gonad are determined by different sets of genes. Our study implicates Cbx2 in testis differentiation through regulating Sry gene expression. ..
- Hacker A, Capel B, Goodfellow P, Lovell Badge R. Expression of Sry, the mouse sex determining gene. Development. 1995;121:1603-14 pubmed..b>Amh expression begins 20 hours after the onset of Sry expression at a time when Sry transcripts are at their peak...
- Behringer R, Cate R, Froelick G, Palmiter R, Brinster R. Abnormal sexual development in transgenic mice chronically expressing müllerian inhibiting substance. Nature. 1990;345:167-70 pubmedMüllerian inhibiting substance (MIS), also known as anti-Müllerian hormone, is a glycoprotein normally secreted by the Sertoli cells of the fetal and adult testis and by granulosa cells of the postnatal ovary...
- Bagheri Fam S, Sim H, Bernard P, Jayakody I, Taketo M, Scherer G, et al. Loss of Fgfr2 leads to partial XY sex reversal. Dev Biol. 2008;314:71-83 pubmed..In summary, we provide evidence that FGFR2 is important for male sex determination in mice, thereby rendering human FGFR2 a candidate gene for unsolved DSD cases such as 10q26 deletions. ..
- Warr N, Bogani D, Siggers P, Brixey R, Tateossian H, Dopplapudi A, et al. Minor abnormalities of testis development in mice lacking the gene encoding the MAPK signalling component, MAP3K1. PLoS ONE. 2011;6:e19572 pubmed publisher..Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans. ..
- Val P, Jeays Ward K, Swain A. Identification of a novel population of adrenal-like cells in the mammalian testis. Dev Biol. 2006;299:250-6 pubmed..These studies reveal the complex nature of steroidogenic cell differentiation during urogenital development. ..
- Gao F, Maiti S, Alam N, Zhang Z, Deng J, Behringer R, et al. The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A. 2006;103:11987-92 pubmed..Our data, along with previous work demonstrating the role of Wt1 at early stages of gonadal development, thus indicate that Wt1 is essential at multiple steps in testicular development. ..
- Al Attar L, Noel K, Dutertre M, Belville C, Forest M, Burgoyne P, et al. Hormonal and cellular regulation of Sertoli cell anti-Müllerian hormone production in the postnatal mouse. J Clin Invest. 1997;100:1335-43 pubmedAnti-Müllerian hormone (AMH) is secreted by immature testicular Sertoli cells. Clinical studies have demonstrated a negative correlation between serum AMH and testosterone in puberty but not in the neonatal period...
- Ottolenghi C, Omari S, Garcia Ortiz J, Uda M, Crisponi L, Forabosco A, et al. Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet. 2005;14:2053-62 pubmed..This suggests the possible continued involvement of sex-determining genes in maintaining ovarian function throughout female reproductive life. ..
- Behringer R, Finegold M, Cate R. Müllerian-inhibiting substance function during mammalian sexual development. Cell. 1994;79:415-25 pubmedTo investigate the role of Müllerian-inhibiting substance (MIS) in mammalian sexual development, we generated MIS-deficient mice...
- Colvin J, Green R, Schmahl J, Capel B, Ornitz D. Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell. 2001;104:875-89 pubmed..While Sry is found only in some mammals, Fgfs are highly conserved. Thus, Fgfs may function in sex determination and reproductive system development in many species. ..
- Chaboissier M, Kobayashi A, Vidal V, Lützkendorf S, van de Kant H, Wegner M, et al. Functional analysis of Sox8 and Sox9 during sex determination in the mouse. Development. 2004;131:1891-901 pubmed..deletion of Sox9 in XY gonads interferes with sex cord development and the activation of the male-specific markers Mis and P450scc, and leads to the expression of the female-specific markers Bmp2 and follistatin...
- Laurich V, Trbovich A, O Neill F, Houk C, Sluss P, Payne A, et al. Müllerian inhibiting substance blocks the protein kinase A-induced expression of cytochrome p450 17alpha-hydroxylase/C(17-20) lyase mRNA in a mouse Leydig cell line independent of cAMP responsive element binding protein phosphorylation. Endocrinology. 2002;143:3351-60 pubmedMüllerian inhibiting substance (MIS) is produced by fetal Sertoli cells and causes regression of the Müllerian duct in male fetuses shortly after commitment of the bipotential embryonic gonad to testes differentiation...
- Tohonen V, Osterlund C, Nordqvist K. Testatin: a cystatin-related gene expressed during early testis development. Proc Natl Acad Sci U S A. 1998;95:14208-13 pubmed..This gene therefore represents one of the putative downstream targets likely to have an essential role in tissue reorganization during early testis development. ..
- Fujimoto Y, Tanaka S, Yamaguchi Y, Kobayashi H, Kuroki S, Tachibana M, et al. Homeoproteins Six1 and Six4 regulate male sex determination and mouse gonadal development. Dev Cell. 2013;26:416-30 pubmed publisher..The regulation of Fog2 induces Sry expression in male sex determination, and the regulation of Nr5a1 in gonadal precursor formation determines gonadal size. ..
- Buaas F, Val P, Swain A. The transcription co-factor CITED2 functions during sex determination and early gonad development. Hum Mol Genet. 2009;18:2989-3001 pubmed publisher..This highlights the gene dosage sensitivity of the pathway's effect on Sry levels and embryonic gonad development...
- Wu R, Zeng Y, Chen Y, Lanz R, Wu M. Temporal-Spatial Establishment of Initial Niche for the Primary Spermatogonial Stem Cell Formation Is Determined by an ARID4B Regulatory Network. Stem Cells. 2017;35:1554-1565 pubmed publisher..Stem Cells 2017;35:1554-1565. ..
- Anttonen M, Ketola I, Parviainen H, Pusa A, Heikinheimo M. FOG-2 and GATA-4 Are coexpressed in the mouse ovary and can modulate mullerian-inhibiting substance expression. Biol Reprod. 2003;68:1333-40 pubmed..g., through activation of the Müllerian-inhibiting substance (MIS) gene expression...
- Siggers P, Carré G, Bogani D, Warr N, Wells S, Hilton H, et al. A novel mouse Fgfr2 mutant, hobbyhorse (hob), exhibits complete XY gonadal sex reversal. PLoS ONE. 2014;9:e100447 pubmed publisher..Fgr2hob is caused by a C to T mutation in the invariant exon 7, resulting in a polypeptide with a mis-sense mutation at position 263 (Pro263Ser) in the third extracellular immunoglobulin-like domain of FGFR2...
- Kim B, Kim Y, Cooke P, Ruther U, Jorgensen J. The fused toes locus is essential for somatic-germ cell interactions that foster germ cell maturation in developing gonads in mice. Biol Reprod. 2011;84:1024-32 pubmed publisher..In summary, we conclude that the Ft locus contains genes essential for somatic-germ cell interactions, without which the germ cell niche fails to mature in both sexes. ..
- Zhang L, Chen M, Wen Q, Li Y, Wang Y, Wang Y, et al. Reprogramming of Sertoli cells to fetal-like Leydig cells by Wt1 ablation. Proc Natl Acad Sci U S A. 2015;112:4003-8 pubmed publisher..This study thus provides a novel concept for somatic cell fate determination in testis development that may also represent an etiology of male infertility in human patients. ..
- Miyado M, Nakamura M, Miyado K, Morohashi K, Sano S, Nagata E, et al. Mamld1 deficiency significantly reduces mRNA expression levels of multiple genes expressed in mouse fetal Leydig cells but permits normal genital and reproductive development. Endocrinology. 2012;153:6033-40 pubmed publisher..The contrastive phenotypic findings between Mamld1 KO male mice and MAMLD1 mutation positive patients would primarily be ascribed to species difference in the fetal sex development. ..
- Ludbrook L, Bernard P, Bagheri Fam S, Ryan J, Sekido R, Wilhelm D, et al. Excess DAX1 leads to XY ovotesticular disorder of sex development (DSD) in mice by inhibiting steroidogenic factor-1 (SF1) activation of the testis enhancer of SRY-box-9 (Sox9). Endocrinology. 2012;153:1948-58 pubmed publisher..In cultured cells, increasing levels of DAX1 antagonized SF1-, SF1/SRY-, and SF1/SOX9-mediated activation of TES, due to reduced binding of SF1 to TES, providing a likely mechanism for DSS. ..
- Mishina Y, Whitworth D, Racine C, Behringer R. High specificity of Müllerian-inhibiting substance signaling in vivo. Endocrinology. 1999;140:2084-8 pubmed..The loss of the uterus and oviducts is consistent with the known activities for MIS. However, it is not clear if the loss of the ovaries in these transgenic females is caused by interactions of MIS ..
- Kaftanovskaya E, Lopez C, Ferguson L, Myhr C, Agoulnik A. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis. FASEB J. 2015;29:2327-37 pubmed publisher..We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation. ..
- Liu C, Bingham N, Parker K, Yao H. Sex-specific roles of beta-catenin in mouse gonadal development. Hum Mol Genet. 2009;18:405-17 pubmed publisher..Our results demonstrate that beta-catenin is responsible for transducing sex-specific signals in the SF1-positive somatic cell population during mouse gonadal development. ..
- Le Bouffant R, Souquet B, Duval N, Duquenne C, Hervé R, Frydman N, et al. Msx1 and Msx2 promote meiosis initiation. Development. 2011;138:5393-402 pubmed publisher..Collectively, our data demonstrate for the first time that some homeobox genes are required for meiosis initiation in the female germ line. ..
- Wittmann W, McLennan I. The male bias in the number of Purkinje cells and the size of the murine cerebellum may require Müllerian inhibiting substance/anti-Müllerian hormone. J Neuroendocrinol. 2011;23:831-8 pubmed publisher..critical periods in cerebellum development occur when the immature testes secrete Müllerian inhibiting substance (MIS; synonym anti-Müllerian hormone) but only trace levels of testosterone...
- Western P, Ralli R, Wakeling S, Lo C, Van Den Bergen J, Miles D, et al. Mitotic arrest in teratoma susceptible fetal male germ cells. PLoS ONE. 2011;6:e20736 pubmed publisher..Further understanding of fetal male germ cell differentiation promises to provide insight into disorders of the testis and germ cell lineage, such as testis tumour formation and infertility. ..
- Miura T, Miura C, Konda Y, Yamauchi K. Spermatogenesis-preventing substance in Japanese eel. Development. 2002;129:2689-97 pubmed..We conclude that eSRS21 prevents the initiation of spermatogenesis and, therefore, suppression of eSRS21 expression is necessary to initiate spermatogenesis. In other words, eSRS21 is a spermatogenesis-preventing substance. ..
- Wittmann W, McLennan I. The bed nucleus of the stria terminalis has developmental and adult forms in mice, with the male bias in the developmental form being dependent on testicular AMH. Horm Behav. 2013;64:605-10 pubmed publisher..0001), and absent in mice that lacked a gonadal hormone, AMH. After 20 days, the number of BNSTp neurons increased in the male mice by 25% (p < 0...
- Vanhoutteghem A, Messiaen S, HervÃ© F, Delhomme B, Moison D, Petit J, et al. The zinc-finger protein basonuclin 2 is required for proper mitotic arrest, prevention of premature meiotic initiation and meiotic progression in mouse male germ cells. Development. 2014;141:4298-310 pubmed publisher..In view of the extreme evolutionary conservation of BNC2, the findings described here are likely to apply to many species. ..
- Smith C, McClive P, Sinclair A. Temporal and spatial expression profile of the novel armadillo-related gene, Alex2, during testicular differentiation in the mouse embryo. Dev Dyn. 2005;233:188-93 pubmed..In the developing testis, its expression profile suggests that Alex2 has a role in specification or development of the interstitial cell lineage. ..
- Spiller C, Wilhelm D, Jans D, Bowles J, Koopman P. Mice Lacking Hbp1 Function Are Viable and Fertile. PLoS ONE. 2017;12:e0170576 pubmed publisher..Lastly, in a model of defective germ cell G1/G0 arrest, the Rb1-knockout model, we found no evidence for Hbp1 mis-regulation, suggesting that the reported RB1-HBP1 interaction is not critical in the germline, despite co-..
- Wilhelm D, Huang E, Svingen T, Stanfield S, Dinnis D, Koopman P. Comparative proteomic analysis to study molecular events during gonad development in mice. Genesis. 2006;44:168-76 pubmed..Moreover, HSC71 was found to be hyperphosphorylated in male compared to female gonads, emphasizing the advantage of the proteomic approach in allowing the detection of posttranslational modifications. ..
- Park S, Zeidan K, Shin J, Taketo T. SRY upregulation of SOX9 is inefficient and delayed, allowing ovarian differentiation, in the B6.Y(TIR) gonad. Differentiation. 2011;82:18-27 pubmed publisher..b>MIS, a marker of Sertoli cells, appeared only in well-organized testis cords...
- Behringer R. The müllerian inhibitor and mammalian sexual development. Philos Trans R Soc Lond B Biol Sci. 1995;350:285-8; discussion 289 pubmed..The müllerian inhibitor currently known as müllerian-inhibiting substance (MIS) or anti-müllerian hormone (AMH), is a member of the transforming growth factor-beta (TGF-beta) family of growth and differentiation factors...
- Allard S, Adin P, Gouédard L, di Clemente N, Josso N, Orgebin Crist M, et al. Molecular mechanisms of hormone-mediated Müllerian duct regression: involvement of beta-catenin. Development. 2000;127:3349-60 pubmed..Apoptosis is also induced by AMH in female Müllerian duct in vitro...
- Tanwar P, Zhang L, Tanaka Y, Taketo M, Donahoe P, TEIXEIRA J. Focal Mullerian duct retention in male mice with constitutively activated beta-catenin expression in the Mullerian duct mesenchyme. Proc Natl Acad Sci U S A. 2010;107:16142-7 pubmed publisherMüllerian-inhibiting substance (MIS), which is produced by fetal Sertoli cells shortly after commitment of the bipotential gonads to testicular differentiation, causes Müllerian duct (MD) regression...
- Smith J, Bowles J, Wilson M, Koopman P. HMG box transcription factor gene Hbp1 is expressed in germ cells of the developing mouse testis. Dev Dyn. 2004;230:366-70 pubmed..We conclude that Hbp1 is up-regulated specifically in germ cells of the developing XY gonad. The expression of Hbp1 in XY germ cells appears to correlate with the onset of mitotic arrest in these cells. ..