{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:23:15Z","timestamp":1792210995969,"version":"4.4.0"},"reference-count":39,"publisher":"The Royal Society","issue":"1333","license":[{"start":{"date-parts":[[1995,11,29]],"date-time":"1995-11-29T00:00:00Z","timestamp":817603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/royalsociety.org\/journals\/ethics-policies\/data-sharing-mining\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,11,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The elegant embryological experiments of Jost demonstrated the existence of a foetal testicular factor that is required to cause the regression of the M\u00fcllerian duct system, the anlagen of the uterus, oviducts and upper portion of the vagina, during male sexual development. The M\u00fcllerian inhibitor currently known as M\u00fcllerian-inhibiting substance (MIS) or anti-M\u00fcllerian hormone (AMH), is a member of the transforming growth factor-\u03b2 (TGF-\u03b2) family of growth and differentiation factors. The genetic manipulation of the mouse germline has lead to the generation of animal models for MIS function. Female transgenic mice that chronically express MIS during embryogenesis are born without a uterus or oviducts and their ovaries lose germ cells and degenerate, recapitulating the phenotype of the bovine freemartin. Some male transgenic mice from very high MIS-expressing lines are feminized, suggesting alterations in androgen biosynthesis. Male mice homozygous for a targeted mutation of the MIS gene develop as male pseudohermaphrodites with both male (testes and Wolffian duct-derived) and female (M\u00fcllerian duct-derived) reproductive organs. Most are infertile because the development of two reproductive systems physically blocks the exit of sperm from these males. In addition, Leydig cell hyperplasia is detected in a proportion of these males and in one case a Leydig cell tumour was found. Recently, a gene encoding a TGF-\u03b2 family type II Ser\/Thr kinase membrane-bound receptor has been isolated that is expressed in both male and female gonads and in the mesenchyme surrounding the M\u00fcllerian ducts during embryogenesis. These findings suggest that MIS-mediated M\u00fcllerian duct regression occurs indirectly through mesenchymal tissue. A targeted mutation of this receptor has been established in the mouse germline. Mice homozygous for this receptor mutation should be useful in understanding the MIS signalling pathway for M\u00fcllerian duct regression and gonadal function.<\/jats:p>","DOI":"10.1098\/rstb.1995.0163","type":"journal-article","created":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T19:03:09Z","timestamp":1166468589000},"page":"285-289","source":"Crossref","is-referenced-by-count":42,"title":["The M\u00fcllerian inhibitor and mammalian sexual development"],"prefix":"10.1098","volume":"350","author":[{"given":"Richard R.","family":"Behringer","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, U. S. 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R.","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"p_3","doi-asserted-by":"crossref","first-page":"7494","DOI":"10.1016\/S0021-9258(18)53202-6","article-title":"Ad 4BP-regulating steroidgenic P-450 gene is a member of steroid hormone receptor superfamily","volume":"268","author":"Honda S.-I.","year":"1993","journal-title":"J. Biol. Chem."},{"key":"p_4","first-page":"125","article-title":"Molecular genetics of the persistent Mullerian duct syndrome, a study of 19 families. Hum. molec","volume":"3","author":"Imbeaud S.","year":"1994","journal-title":"Genet."},{"key":"p_5","first-page":"1","article-title":"Anti-Miillerian hormone, the Jost factor","volume":"48","author":"Josso N.","year":"1993","journal-title":"Recent Prog. Horm. Res."},{"key":"p_6","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0290349"},{"key":"p_7","doi-asserted-by":"publisher","DOI":"10.1038\/351117a0"},{"key":"p_8","doi-asserted-by":"crossref","unstructured":"Knebelmann B. Boussin L. Guerrier D. etal 1991 Anti-Mullerian hormone Bruxelles a non-sense mutation in the last exon of the anti-Mullerian hormone gene associated with the persistent Mullerian duct syndrome in three","DOI":"10.1073\/pnas.88.9.3767"},{"key":"p_9","unstructured":"N a t u r e Lond. 345 167-170. brothers. Proc. natn. Acad. Sci. U.S.A. 88 3767-3771."},{"key":"p_10","first-page":"1","article-title":"Kreidberg, J. A., Sariola, H., Loring, J. M. al. 1993 Mullerian-inhibiting substance function during mammalian sexual development","volume":"79","author":"Behringer R. R.","year":"1994","journal-title":"Cell"},{"key":"p_11","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90601-A"},{"key":"p_12","doi-asserted-by":"publisher","DOI":"10.1007\/BF00220465"},{"key":"p_13","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90783-X"},{"key":"p_14","doi-asserted-by":"crossref","unstructured":"Cate R. L. Donahoe P. K. & MacLaughlin D. T. 1990 Mullerian inhibiting substance. In Peptide growthfactors and their receptors vol.II (ed. M. B. Sporn & A. B. Roberts) pp. 179-210. Berlin: Springer-Verlag.","DOI":"10.1007\/978-3-642-74781-6_7"},{"key":"p_15","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-4-573"},{"key":"p_16","first-page":"1006","article-title":"Cloning, expression and alternative splicing of the receptor for anti-Mullerian hormone","volume":"8","author":"di Clemente N.","year":"1994","journal-title":"Molec. Endocr."},{"key":"p_17","first-page":"431","article-title":"Mullerian inhibiting substance, gene structure and mechanism of action of a foetal regressor","volume":"43","author":"Donahoe P. K.","year":"1987","journal-title":"Recent Prog. Horn. 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