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The growth of an organism involves the proliferation and migration of cells within an extracellular matrix. As a cell surface receptor, the Dag1 gene product dystroglycan links the intracellular cytoskeleton to the extracellular basement membrane in many cells. Thought to act as a structural protein dystroglycan may also participate in signal transduction. This study aims to better understand the role of dystroglycan during kidney morphogenesis. I hypothesised that a lack of dystroglycan in the precursor cells of the kidney could lead to altered kidney growth. Chimaeric mice deficient in dystroglycan were generated to test this hypothesis. A total of 38 chimaeras had genetic contribution and histological analysis performed on their kidneys. Of the chimaeras analysed, only four demonstrated altered kidney morphology. Further histological, immunohistochemical and biochemical studies established whether a link existed between this morphology and a deficiency in dystroglycan. Normal laminar architecture and nephrotic structures of the kidneys suggest that normal kidney organogenesis occurred in the absence of dystroglycan. The pattern and expression level of basement membrane components suggests that normal basement membrane formation also occured in the absence of dystroglycan. Biochemical analysis revealed that although dystroglycan protein levels correlate with the genetic contribution of the chimaeric kidney, it does not correlate with the altered morphology. Ureter blockage causing hydronephrosis can explain the morphology observed. A deficiency of dystroglycan in the ureter may in turn have caused this blockage. These findings suggest that dystroglycan is not necessary for kidney organogenesis, since kidney development occurred normally in all 38 chimaeric animals irrespective of genetic contribution.

Cimetidine is a histamine H2-receptor antagonist that is among the most widely prescribed drugs in the world. In addition to its inhibitory action on gastric acid secretion, a possible role in kidney tubulointerstitial disease has been suggested. Isolated reports have also suggested an association between cimetidine administration and acute interstitial nephritis. The present study examined the effect of cimetidine on renal function in the rat. The nine rats used in this study had normal renal function and urinalyses before treatment with cimetidine. The cimetidine treated rats then developed a clinical picture of weakness, hematuria, proteinuria, casturia, oliguria, and increases in serum blood urea nitrogen and creatinine.Following the 6 weeks treatment period, all rats were sacrificed and their kidneys prepared for microscopic study. Histologically, the patchy, intense tubulointerstitial infiltration of lymphocytes, plasma cells, and other cells observed in the cortex of the rat kidneys is quite similar to findings described in human cases of drug-induce hypersensitivity tubulointerstitial disease. In addition, other pathologic conditions which can cause tubulointerstitial disease were adequately ruled out. Specifically, bacterial pyelonephritis was excluded as a result of the consistently sterile urine test. In conclusion, the author feels that the clinical, aboratory, and histologic findings in this study strongly suggests an association between of tubulointerstitial disease and the use of cimetidine. / Department of Physiology and Health Science

Thesis (PhD)--University of South Australia, 2003.

x, 101 leaves : ill., tables, graphs ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1981) from the Dept. of Obstetrics and Gynaecology, University of Adelaide

Thesis (Ph.D. 1981) from the Department of Obsetetrics and Gynaecology, University of Adelaide.

Thesis (Ph.D.) -- University of Western Sydney, 2001. / "Thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy, University of Western Sydney, School of Nursing, Family and Community Health" Bibliography : leaves 315-342.

Thesis (Ph.D.)--University of Western Australia, 2005.