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Mechanism of sex determination and reversal in an XY mouse strain

Sry on the Y-chromosome triggers the fetal gonad to begin differentiation into testis in mammals. Mutation or absence of Sry results in development of ovaries and the female phenotype. However, XY sex reversal in the presence of wild-type Sry exists in mice and man. One such example is the B6-YTIR mouse, whose autosomes and X-chromosome are of the C57BL6/J mouse (Mus musculus molossinus) whereas the Y-chromosome is from a mouse originating in Tirano, Italy (Mus musculus domesticus). B6-YTIR mice develop only ovaries or ovotestes in fetal life. The objective of my thesis was to identify the mechanism of sex reversal in the B6-YTIR mouse. The results indicate that onset of Sry transcription in B6-YTIR gonads is comparable to control B6 XY gonads. On the other hand, onset of Mis, 17alpha-HA, 3beta-HSD (testicular cell products), p450arom as well as inactivation of Sry transcription are delayed or absent in the sex reversed gonads. It has been suggested that low levels of Sry transcription may account for aberrant testis differentiation in B6-YTIR mice. We observed relatively low levels of Sry transcripts not only in B6-YTIR but also in B6 mice. However, levels in normal B6-YSJL mice were significantly greater. On the SJLB6F1 background, where no sex reversal occurs, Sry transcript levels of the TIR allele increased while those of B6 and SJL alleles remained the same as in the B6 background. Thus, low levels of Sry transcript from the B6 allele are sufficient whereas the levels from TIR and SJL alleles (both DOM type) appear to be critical for testis determination. We then compared the levels of endogenous Sry proteins. A combination of immunoprecipitation and immunoblotting succeeded in detecting a protein band whose expression profile and molecular size are consistent with those of the predicted Sry. Sry protein levels in B6-Y TIR gonads were roughly two fold greater than in B6 XY gonads. We hypothesize that the Sry protein of the TIR/SJL alleles is less efficient

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.38073
Date January 2001
CreatorsLee, Chung-Hae, 1966-
ContributorsTaketo, Teruko (advisor)
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageDoctor of Philosophy (Department of Biology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001846289, proquestno: NQ75652, Theses scanned by UMI/ProQuest.

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