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Title: A genetic modifier of B6.YPOS gonadal sex reversal on chromosome 13
Author: Livermore, Catherine
ISNI:       0000 0004 7966 1839
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Sex determination is the process by which the embryonic gonad differentiates into either a testis or an ovary. When the mammalian gonad first arises in the embryo, the cells comprising it are bipotential: they can adopt a testiscular or ovarian fate. Such commitment is governed chromosomally, principally by the presence or absence of the Y chromosome. Testis determination in the mouse is initiated by the expression of the Y-linked gene, Sry. The timing of Sry expression is critical: if there is any delay in the onset of expression, such that a threshold level is not reached before 11.5 days post coitum (dpc), then the outcome will be XY ovotestis or ovary development. Disrupted Sry expression and gonadal sex reversal can arise due to mutations in genes encoding key regulators (WT1, GATA4, MAP3K4, GADD45γ etc.) and also from a putative functional 'mismatch' between the Y chromosome and the autosomes/X chromosome. Such a situation arises following introgression of the domesticus Y chromosome of Mus poschiavinus into the C57BL/6J (B6) genetic background, resulting in so-called B6.YPOS sex reversal. While examining the molecular basis of B6.YPOS sex reversal, a region of chromosome 13 in the B6.YPOS colony at MRC Harwell was found to be heterozygous for sequences not derived from B6. This region modifies the B6.YPOS sex reversal phenotype, promoting testis development and male fertility. This thesis describes experiments aimed at understanding this locus, attempting to identify its origins, and elucidating the mechanism by which it acts. It also reports on an investigation into the genes within the region and their possible role in sex determination.
Supervisor: Greenfield, Andy Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available