Investigations of Ocular Melanosis in Cairn Terriers

Simon Petersen-Jones DVetMed PhD DVOphthal DipECVO MRCVS
Department of Small Animal Clinical Sciences
Michigan State University D-208
Veterinary Medical Center
East Lansing MI 48864-1314

Aims for our studies

1. Completely characterize the disease, Ocular Melanosis, so that we know all the variations of the disease and the range of ages at which dogs can develop the lesions of Ocular Melanosis.
2. Prove beyond doubt the mode of inheritance of Ocular Melanosis.
3. Identify the genetic defect that causes Ocular Melanosis and develop a DNA test for that mutation. Identify the most effective treatment for dogs that do develop the condition.

Progress report

We now have 191 DNA samples from Cairn Terriers of which 93 are from dogs affected with Ocular Melanosis and the remainder are from relatives of dogs with Ocular Melanosis (OM). We have pedigree information on all of the dogs except for one or two where pedigrees were not available. The individual pedigrees have been drawn up into large pedigrees linking affected dogs to help us better analyze the mode of inheritance. We have been able to rule out some modes of inheritance and although we have a theory of the mode of inheritance we are still not yet able to prove our theory beyond any doubt. We have been performing special examinations of eyes removed from OM dogs with glaucoma. This uses a technique called immunohistochemistry, which uses a special staining technique utilizing antibodies to stain the histological sections. By seeing which different antibodies stain the cells that proliferate in Ocular Melanosis we can determine in detail exactly what type of cell they are. By completely characterizing the cell type this can give us information about the type of gene that may be mutated to cause the disease. We are also looking at some eyes by electron microscopy. This technique gives a very high power view of the cells and seeing the ultrastructure of these cells also helps us to work out the type of cell that is proliferating. These techniques are expensive and we have only been able to afford to do preliminary studies. We need more funding to allow us to fully utilize these techniques

Our plans for the future:

We are fortunate to have funding for a graduate student to work on Ocular Melanosis starting full time for one year in January 2005. We need some matching funding from the Cairn Terrier Club of America to allow our graduate student to do the studies needed to reach our aims. If we cannot raise the money to fund this work we will need to move her to a different project.

1. Further immunohistochemistry of eyes from affected dogs to allow the cell type involved to be characterized.
2. Further electron microscopy of eyes from affected dogs to allow the cell type involved to be characterized.
3. Mapping of hte location of the OM mutation in the canine genome. This will be a genome–wide mapping project. We feel that we now have sufficient DNA samples to enable this approach to be used (however further samples will increase the chances of success).
4. Once the location is mapped we will need to sequence genes in that regions to see which gene has the mutation causing ocular melanosis.

What we need:

1. Blood samples from OM affected dogs and as many as possible of their immediate relatives
2. DNA samples from as many different Cairn Terriers as possible. For this part of the project we can work from cheek swabs. This will make it easier and cheaper to collect the samples. A pedigree and any eye examination report will also be needed.
3. Eyes removed from affected dogs. We need to be contacted before the eye is removed as for some investigations (such as immunohistochemistry and electron microscopy) because the eyes need to be treated in a specific manner. For these studies regular fixation is not suitable.
4. Funding to support the studies. We have funding to cover the major costs of these investigations i.e. stipend costs of our graduate student. However the costs of gene mapping, immunohistochemistry and electron microscopy are substantial. We sincerely hope that we can make full use of the opportunity that having a graduate student to work on the project offers us.

We are very keen to make major progress towards our ultimate aim of developing a DNA test for OM. We are willing to speak to breeders, take part in screening sessions or examine potentially affected dogs at MSU.