Congenital cataract is a common cause of blindness in children; however, its pathogenesis remains unclear. Genetic factors have been shown to play an important role in the pathogenesis of congenital cataract. The current genetic models of congenital cataract include autosomal dominant, autosomal recessive, and sex-linked inheritance. Sex-linked congenital cataract could be inherited through the...

Alport syndrome (AS) is an inherited type IV collagen nephropathies characterized by microscopic hematuria during early childhood, the development of proteinuria and progression to end-stage renal disease. Since choosing the right therapy, even before the onset of proteinuria, can delay the onset of end-stage renal failure and improve life expectancy, the earliest possible differential diagnosi...

Collagen IV is a major structural component of all basal laminae (BLs). Six collagen IV alpha chains are present in mammals; alpha 1 and alpha 2(IV) are broadly expressed in embryos and adults, whereas alpha 3-6(IV) are restricted to a defined subset of BLs. In the glomerular BL of the kidney, the alpha 1 and alpha 2(IV) chains are replaced by the alpha 3-5(IV) chains as development proceeds. I...

The clinical implications of thin basement membrane nephropathy (TBMN) in renal transplantation must be considered from the perspectives of both the allograft recipient and the donor. Most individuals with TBMN have a benign course, but some develop end-stage renal failure (ESRF) and undergo transplantation. ESRF in patients with TBMN often results from the presence of additional glomerular or ...

Identification of a Mutation in COL4A5 Causative for X-linked Alport Syndrome in the Domestic Dog and Analysis of Gene Expression in the Kidneys of Affected and Nonaffected Siblings. (December 2003) Melissa Luanne Cox, B.Sc., Dalhousie University Chair of Advisory Committee: Dr. Keith E. Murphy The domestic dog, Canis lupus familiaris, plays many roles in the lives of humans. Additionally, the ...

X-linked Alport syndrome (XLAS) is a progressive disorder of basement membranes caused by mutations in the COL4A5 gene, encoding the alpha5 chain of type IV collagen. A mouse model of this disorder was generated by targeting a human nonsense mutation, G5X, to the mouse Col4a5 gene. As predicted for a nonsense mutation, hemizygous mutant male mice are null and heterozygous carrier female mice ar...