This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Al-Shawi, R Articles by Bishop, J O Search for Related Content PubMed PubMed Citation Articles by Al-Shawi, R Articles by Bishop, J O

 Previous Article  |  Next Article 

Mol Cell Biol. 1988 November; 8(11): 4821-4828

A Mup promoter-thymidine kinase reporter gene shows relaxed tissue-specific expression and confers male sterility upon transgenic mice.

R Al-Shawi, J Burke, C T Jones, J P Simons and J O Bishop

Department of Genetics, University of Edinburgh, Scotland.

ABSTRACT

A hybrid gene was made by fusing the 2.2-kilobase 5' promoter region of a mouse group 1 major urinary protein (Mup) gene to the coding region of the herpes simplex virus type 1 thymidine kinase gene (HSV tk) and introduced into the genomes of mice by microinjection. Transgenic G0 males were sterile, or when fertile did not transmit the foreign gene, and the transgenic male descendants of G0 females were also sterile. Seven "lines" were established by breeding from G0 females and their transgenic female descendants. Six lines expressed HSV thymidine kinase activity in the liver, and activity correlated perfectly with the presence of HSV tk RNA. In three of four lines examined, expression was lower in female than in male liver, and in these lines the same sex difference was observed in the rate of run-on transcription of the foreign genes in liver nuclei. When females of one of the sexually dimorphic lines were treated with testosterone, the levels of HSV tk RNA and thymidine kinase activity were increased, although not to male levels. In these aspects of liver expression, and also in a lack of expression in seven other tissues, the hybrid gene exhibits many of the characteristics of an endogenous group 1 Mup gene. However, the gene was also expressed (at high levels) in the preputial gland and testis, two tissues in which Mup genes are not expressed. The gene, when introduced into five of the seven lines, carried a copy of the Escherichia coli supF gene attached beyond the 3' end of the HSV tk gene, but this did not affect the overall expression pattern. All of the lines were male sterile and expressed HSV thymidine kinase in the testis, but one line showed no activity in the liver, and another showed none in the preputial gland. Testicular expression is therefore the likely cause of sterility. Data are described which suggest that the causes of misexpression in the preputial gland and testis are different. Since expression in each tissue occurred in several lines, the structure of the hybrid gene must be responsible in each case. Five intensively studied lines showed at least four consistently different patterns of relative expression in preputial gland, testis, male liver, and female liver. These differences do not correlate in any way with the copy number of the foreign gene in the different lines and must be due to some other aspect of line specific integration.

---

Mol Cell Biol. 1988 November; 8(11): 4821-4828

This article has been cited by other articles:

• Srichai, M. B., Hao, C., Davis, L., Golovin, A., Zhao, M., Moeckel, G., Dunn, S., Bulus, N., Harris, R. C., Zent, R., Breyer, M. D. (2008). Apoptosis of the Thick Ascending Limb Results in Acute Kidney Injury. J. Am. Soc. Nephrol. 19: 1538-1546 [Abstract] [Full Text]  
• Jalabi, W., Boehm, N., Grucker, D., Ghandour, M. S. (2005). Recovery of Myelin after Induction of Oligodendrocyte Cell Death in Postnatal Brain. J. Neurosci. 25: 2885-2894 [Abstract] [Full Text]  
• Osipovich, A. B., Singh, A., Ruley, H. E. (2005). Post-entrapment genome engineering: First exon size does not affect the expression of fusion transcripts generated by gene entrapment. Genome Res 15: 428-435 [Abstract] [Full Text]  
• Cerrato, F., Sparago, A., Matteo, I. D., Zou, X., Dean, W., Sasaki, H., Smith, P., Genesio, R., Bruggemann, M., Reik, W., Riccio, A. (2005). The two-domain hypothesis in Beckwith-Wiedemann syndrome: autonomous imprinting of the telomeric domain of the distal chromosome 7 cluster. Hum Mol Genet 14: 503-511 [Abstract] [Full Text]  
• Chen, Y.-T., Levasseur, R., Vaishnav, S., Karsenty, G., Bradley, A. (2004). Bigenic Cre/loxP, pu{Delta}tk conditional genetic ablation. Nucleic Acids Res 32: e161-e161 [Abstract] [Full Text]  
• Tian, B., Han, L., Kleidon, J., Henke, C. (2003). An HSV-TK Transgenic Mouse Model to Evaluate Elimination of Fibroblasts for Fibrosis Therapy. Am. J. Pathol. 163: 789-801 [Abstract] [Full Text]  
• Shen, S., Spratt, C., Sheward, W. J., Kallo, I., West, K., Morrison, C. F., Coen, C. W., Marston, H. M., Harmar, A. J. (2000). Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice. Proc. Natl. Acad. Sci. USA 97: 11575-11580 [Abstract] [Full Text]  
• Furuchi, T, Masuko, K, Nishimune, Y, Obinata, M, Matsui, Y (1996). Inhibition of testicular germ cell apoptosis and differentiation in mice misexpressing Bcl-2 in spermatogonia. Development 122: 1703-1709 [Abstract]  
• Wilkie, T M, Braun, R E, Ehrman, W J, Palmiter, R D, Hammer, R E (1991). Germ-line intrachromosomal recombination restores fertility in transgenic MyK-103 male mice.. Genes Dev. 5: 38-48 [Abstract]