Basement membrane composition of Dag1 null chimaeric mice kidneys

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