Lye, C.M.; (2008) Teashirts in the mammalian urinary tract. Doctoral thesis , University of London.

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Abstract

Teashirt genes encode putative transcription factors, and were first identified in Drosophila melanogaster. Teashirt genes regulate various aspects of Drosophila and vertebrate embryonic development, and there is evidence of functional conservation of Teashirts between species. Since Teashirt genes are expressed during (and may play a role in) the development of the Drosophila renal system, I hypothesised that Teashirt genes play a role in the development of the mammalian renal system/urinary tract. To investigate this possibility I sought the expression of the mouse Teashirt genes (mTshzl, mTshz2 and mTshz3) in the kidneys of mice at various stages of development using polymerase chain reaction based methods. I found that all mouse Teashirt genes were expressed in metanephric kidneys from inception and through their maturation, findings consistent with my hypothesis. In order to develop reagents to further define the expression patterns of Teashirt genes in urinary tracts (including kidneys) of embryonic and adult mice I had polyclonal antibodies designed and generated to specifically recognise proteins encoded by mTshzl, mTshz2 and mTshz3, and tested their reactivity and specificity. Secondly, I used a mutant mouse (in which mTshz3 had been inactivated by replacing the majority of its coding sequence with a lacZ reporter construct) to investigate the expression and function of mlshz3 in the urinary tract. By following lacZ expression in heterozygous transgenic mice, I found that mTshz3 was expressed in kidney medullary stroma, and in mesenchymal cells of the ureters and urinary bladder. Homozygous (mTshz3 null) transgenic mice displayed a striking, bilateral hydronephrosis and hydroureter phenotype. I showed that this phenotype develops due to a failure of ureteric smooth muscle differentiation, leading to defective peristalsis, and therefore urine accumulates in the proximal ureter and renal pelvis. Thus mTshz3 is required during mouse urinary tract development for the differentiation of ureteric smooth muscle.

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