title: Sex reversal caused by Mus musculus domesticus Y chromosomes linked to variant expression of the testis-determining gene Sry.
abstract: When the Y chromosomes from certain populations of Mus musculus domesticus are introduced into the mouse strain C57BL/6 (B6), testis determination can fail, resulting in gonads developing either as ovotestes (with both ovarian and testicular components) or as ovaries. Not all Y(DOM) chromosomes cause sex reversal. Y(DOM) chromosomes are divided into three classes based upon their ability to induce testes in B6. The molecular basis underlying the three Y(DOM) classes is an enigma. The simplest explanation is that they harbor different alleles of the testis-determining gene, Sry. Sequencing of Sry(DOM) genes has indeed identified polymorphisms. However, none were unequivocally linked to the sex-reversal trait. It was concluded that all SRY(DOM) proteins are functionally equivalent. Using a semiquantitative RT-PCR assay, we now show that representatives of the three Y(DOM) classes have variant Sry expression patterns, that severity of sex reversal correlates with Sry mRNA titers, and that genetic correction of the sex reversal results in the upregulation of Sry expression. We propose that the variant Sry expression patterns result from polymorphisms at the site of a putative Sry enhancer.
authors.affiliation: Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232-2175, USA. claude.nagamine@mcmail.vanderbilt.edu
authors.forename: C M
authors.initials: CM
authors.lastname: Nagamine
authors.forename: K
authors.initials: K
authors.lastname: Morohashi
authors.forename: C
authors.initials: C
authors.lastname: Carlisle
authors.forename: D K
authors.initials: DK
authors.lastname: Chang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D012734:Disorders of Sex Development; D018628:Gene Dosage; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051876:Sex-Determining Region Y Protein; D019170:Somites / Q000378:metabolism; D013737:Testis / Q000196:embryology* / Q000254:growth & development; D014157:Transcription Factors; D014998:Y Chromosome / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C501500:Rbmy protein, mouse; D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse; D014157:Transcription Factors