Juvenile renal dysplasia (JRD), also referred to as juvenile nephropathy, is an important category of kidney diseases in canines. Dysplasia is defined as abnormal growth or development of cells or organs. In the case of JRD the kidney fails to develop properly during embryogenesis in the womb. At birth immature structures consisting of undifferentiated fetal cells or tissue types are found in the kidney, and are persistent throughout the life of the animal.

Many breeds of dogs are afflicted with JRD, and this has been documented in both veterinary text books, as well as case reports and articles in the scientific literature(see: breeds with rd). Of note is that JRD in these breeds share a common phenotype, characterized by immature glomeruli, and/or tubules and persistent mesenchyme. Given the evolution of the domestic dog it would not be surprising if the disease causing mutation for JRD is conserved among the various breed. In fact this has been shown to be true for type I von Willebrands disease, and epilepsy . The recently discovered mutation for a form of epilepsy in dogs has also been found in wolves.

The morphological features of JRD in dogs differ slightly from those in man, and therefore selection of genes that are responsible for this disease is somewhat difficult.

During the development of the fetus, certain genes act in a pathway or cascade to direct the development of the various organs and structures that make up the body (think of it as dominos:if one domino is missing the other ones wont perform their task in the array). Since every cell contains two copies of every gene, one non-mutated copy may be sufficient to complete to cascade (recessive inheritance). The human genome contains about 20,000 to 25,000 genes, and the canine genome is likely to contain about the same number. Of these several hundred or more may be dedicated to the maturation of specific organs. Not all of these “tissue specific” genes are absolutely essential to the development of specific cell types, as has been shown in “knockout mice”, where genes have been completely eliminated with no observable effect on the animal. In the case of renal dysplasia in model organisms such as the mouse, mutated transcription factors (genes that code for proteins that turn on other genes) or growth factors (genes that code for proteins that promote the growth of cells), have been implicated in causing the disease(Ref).

The mode of inheritance of JRD has been widely debated, as this disease can present itself with a wide range of symptoms and pathological findings. Definitive diagnosis of JRD is done by a wedge biopsy which reveals dysplastic lesions, including abnormal ducts, and glomeruli. Individuals with an abnormal biopsy can be asymptomatic, showing no signs of the disease, On the other hand, they may present with classic signs of chronic end stage renal failure (4), or somewhere between these two extremes. Given this broad spectrum of symptoms affected individuals often go unnoticed, and remain in the breeding population. This is why development of a genetic test is critical to the management and elimination of this disease. Further a genetic test will shed light on the mode inheritance.

The purpose of this research is to examine possible candidate genes in the above categories that are known to be expressed in a spatial and temporal manner in the developing kidney within the structures that are ultimately affected in animals with JRD. The ultimate goal is to find a disease causing mutation, and develop a genetic test for management and elimination of this disease (see : kinds of genetic tests). Only a direct test is acceptable for proper management of this disease.