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Gene expression during testis determination in the mouse

Hacker, Adam Michael; (1995) Gene expression during testis determination in the mouse. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Sry, the Y linked testis determining gene, is expressed in the germ cells of the adult testis and somatic cells of the developing gonad. RNase protection analysis has been used to define the transcripts expressed in these tissues. In the adult testis two transcripts are present, a long RNA molecule, which includes part of both 5' and 3' arms of the inverted repeat spanning the Sry locus, and a 1.23 kb circular RNA. The transcript in the genital ridge is a conventional single exon of 4.9 kb initiating within the unique region of the Sry locus and extending into the 3' arm of the inverted repeat. Knowledge of this transcript allows predicts to be made concerning the protein product, reveals several features which may be involved in translational control and pinpoints the position of the promoter region. The timing of Sry expression has also been examined using RNase protection as a quantitative technique on accurately staged samples. Sry transcripts are first detectable just after 10.5 days post coitum (dpc), they reach a peak at 11.5 days and then decline sharply so that none are detected 24 hours later. The expression of other genes, including anti-Müllerian hormone (Amh) and Sox-3, have also been analysed carefully. Amh is the first known marker of Sertoli cell differentiation and has been proposed as a candidate target gene for the direct action of SRY. Amh expression begins 20 hours after the onset of Sry expression at a time when Sry transcripts are at their peak. While this does not prove a direct interaction between the two genes, it defines the critical period during which Sry must act to initiate Sertoli cell differentiation. Sox-3 shows the greatest degree of homology to Sry and maps to the X chromosome. In addition to being expressed in the developing central nervous system, Sox-3 transcripts are present at the same or even at a greater level than Sry in the non-germ cell portion of the genital ridge. These data imply that Sox-3 may be the evolutionary ancestor to Sry and may have a role in sex determination. An investigation of the upstream region of Amh revealed the presence of an ubiquitously expressed gene encoding a spliceosome accessory protein, SAP62. The organization of the gene, including a possible transcriptional start site and polyadenylation site, has been determined. The mouse Amh and Sap62 transcription units are separated by only 309 bp. Sap62 is unlikely to have any specific role in sex determination but may influence the expression of Amh.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Gene expression during testis determination in the mouse
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10103129
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