What Have We Learned From The Colony Dogs?

Dr. Shelly Vaden, September 28, 2006

It has been twelve years since the first dogs were born into our colony of dogs for the study of PLE and PLN in Soft Coated Wheaten Terriers. These dogs were bred with several goals in mind. So what have we accomplished and where do we need to go?

The first goal was to determine the mode of inheritance of this disorder. In order to do this, one of our affected male SCWT dogs was bred to a Beagle to create Wheagles. These dogs were then sequentially evaluated over time. Some of the Wheagles developed overt disease. This would suggest that the disease is inherited as a dominant trait. However, the prevalence of disease within the colony of purebred SCWT dogs is high, supportive of an autosomal recessive mode of inheritance. Determination of the exact mode of inheritance may require a second outcross breeding to a dog of a breed other than a SCWT or a Beagle. At this point in time, we cannot say with certainty that Beagles do not have a similar abnormality that is complicating the phenotypic expression of PLE and PLN in our Wheagles. DNA has been harvested from all of our dogs. It is also possible that if a genetic marker for this disease is discovered, we will be able to confirm the mode of inheritance through application of the marker.

Our second goal was to sequentially evaluate dogs to gain a better understanding of the development of clinical signs of this disease, so that we could make better recommendations for screening SCWTs. We have been able to effectively achieve this goal. We know that increases in fecal API are prevalent throughout the colony (and the general population of SCWTs). These precede the onset of PLN. However overt PLE, as manifested by decreased serum protein concentrations, does not always precede the onset of PLN. Those dogs developing overt PLE had significantly greater number of fecal API samples >15 ug/g. This information is very useful because it suggests that the enteric disease may have a pathogenic role in the renal disease, as suspected. It has also helped us to establish that to be an effective screening tool, evaluation of fecal API must be initiated in dogs that are less than 3 years of age and continued annually lifelong. We have worked with investigators at Texas A&M to longitudinally evaluate the prevalence of increased fecal API in apparently normal dogs who do not have overt signs of enteric disease. This study has allowed us to generate more refined recommendations for breeders and pet owners. As for PLN, we found that microalbuminuria is highly prevalent in SCWTs of our colony. It often precedes the onset of increased urine protein: creatinine ratios, which is a standard test used to screen dogs for proteinuria. Some dogs of our colony had sporadic microalbuminuria and some have increased values that are not progressively increasing. However, we know that microalbuminuria that is persistent and of increasing magnitude is the best early predictor of PLN.

We have also been evaluating the therapeutic benefit of sodium cromoglycate administration and hydrolysate diet consumption in the affected SCWTs of our colony. This has been a more difficult study to perform because our other objectives require that we follow the disease to a later state than which we might generally intervene therapeutically by today’s standards. However, even in these later stages of disease, it appears as if there may be a beneficial effect of these interventions in some dogs. It must be also noted that individual dogs may not respond. More dogs need to be entered into the treatment study to determine if these effects are real and to determine what are the identifiable differences between responders and non-responders. We have determined that treatment with Vivonexâ or other elemental diet helps alleviate the severe manifestations of PLE. It would be great to apply these findings to a large clinical study of SCWTs in the general population who are affected with PLE or PLN or both. As a final part of these studies, we have been feeding a litter of dogs a hydrolysate diet since weaning. Although it is still too early to say, it appears that this diet may delay the onset of PLE, and possibly PLN, but probably does not prevent the disease. However, this data is preliminary and absolute conclusions cannot be made at this time. Furthermore, direct applications of these findings to the general population of dogs will be difficult.

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Updated 10/20/06.