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Title: Male sterility in transgenic mice caused by expression of herpes simplex type 1 virus thymidine kinase
Author: Burke, Joanne
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1993
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The mouse major urinary proteins (MUPs) are encoded by a family of about 35 genes. The expression of the genes is under complex tissue-specific, developmental and hormonal control. Four groups of Mup genes have been identified, the largest of which are the group 1 genes and the inert group 2 pseudogenes. Most group 1 genes are expressed exclusively in the liver, while a small subset are also expressed in the mammary glands of females. In an attempt to identify the regions in Mup genes which lead to their tissue specificity and hormone responses, transgenic mice were generated containing the 2.2 kb 5' promoter region of a mouse Mup group 1 gene (BS6) linked to the coding region of the herpes simplex virus type 1 thymidine kinase gene (HSV1-tk). HSV1 thymidine kinase (HSV1-TK) assays revealed that the hybrid gene was expressed in the liver of 4 of the 5 transgenic lines examined, with expression first being detected at just over 2 weeks of age. In 3 of the 4 expressing lines examined expression was lower in female than male livers and when females of one of the sexually dimorphic lines were treated with testosterone, levels of HSV1-TK activity were elevated, although not to male levels. In these aspects of liver expression, the transgene exhibited many of the characteristics of the endogenous group 1 Mup genes. However, the transgene was also consistently expressed at high levels in the preputial gland and testis. This is unexpected since Mup genes are not expressed in either tissue. Evidence is presented here which suggests that the causes of misexpression in the preputial gland and testis are different. Testicular misexpression is independent of the attached tissue-specific promoter, and is observed in transgenic lines containing a promoterless HSV1-tk gene.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available