Multi-Drug Resistance Gene (MDR) codes for a protein that is responsible for protecting the brain by transporting potentially harmful chemicals away. In certain breeds, a mutation occurs in the MDR1 gene that causes sensitivity to Ivermectin, Loperamide, and a number of other common drugs. Dogs with this mutation have a defect in the P-glycoprotein that is normally responsible for transporting certain drugs out of the brain. The defective protein inhibits the dog's ability to remove certain drugs from the brain, leading to a buildup of these toxins. As a result of the accumulation of toxins, the dog can show neurological symptoms, such as seizures, ataxia, or even death.
Dogs that are homozygous for the MDR1 gene (meaning that they have two copies of the mutation) will display a sensitivity to Ivermectin and other similiar drugs. These dogs will also always pass one copy of the mutation to all potential offspring. Dogs that are heterozygous (meaning they have only one copy of the mutation) can still react to these drugs at higher doses. Also, there is a 50% chance that a dog with one copy of the mutation will pass it on to any offspring.
There are many different types of drugs that have been reported to cause problems. The following is a list of some of the drugs:
Ivermectin (found in heartworm medications)
Loperamide (Imodium over the counter antidiarrheal agent)
Doxorubicin
Vincristine
Vinblastine (anticancer agents)
Cyclosporin (immunosuppressive agent)
Digoxin (heart drug)
Acepromazine (tranquiliser)
Butorphanol ("Bute" pain control)
The following drugs may also cause problems:
Ondansetron
Domperidone
Paclitaxel
Mitoxantrone
Etoposide
Rifampicin
Quinidine
Morphine
Multi-Drug Resistance Gene (MDR1)
Collie eye anomaly, also referred to as collie eye defect, is an inherited congenital condition. The chromosomes that determine the development of the eyes are mutated, so that the choroid (the collection of blood vessels that absorb scattered light and nourish the retina) is underdeveloped. The mutation can also result in other defects in the eye with more severe consequences, such as retinal detachment. When this mutation does occur, it is always in both eyes, although it might be more severe in one eye than the other. Approximately 70 to 97 percent of rough and smooth collies in the United States and Great Britain are affected, and approximately 68 percent of rough collies in Sweden are affected. Border Collies are also affected, but at a much lower two to three percent. It is also seen in Australian Shepherds, Shetland Sheepdogs, Lancashire Heelers, and other herding dogs.
Symptoms and Types
While a veterinarian can determine through genetic analysis whether your dog has this defect, there may be no symptoms, until the onset of blindness signals you to the problem. There are stages of this disease, some more obvious that others, that lead up to the final outcome. Some associated conditions that may occur with this defect are microphthalmia, where the eyeballs are noticeably smaller than normal; enophthalmia, where the eyeballs are abnormally sunken in their sockets; anterior corneal stromal mineralization -- that is, the connective tissue of the cornea (the transparent coat at the front of the eye) has become mineralized, and shows as a cloud over the eyes; and an effect that is less obvious on inspection, retinal folds, where two layers of the retina do not form together properly.
Causes
The cause of collie eye anomaly is a defect in chromosome 37. It only occurs in animals that have a parent, or parents, that carry the genetic mutation. The parents may not be affected by the mutation, and may therefore not have been diagnosed with the abnormality, but offspring can be affected, especially when both parents carry the mutation. It is also suspected that other genes may be involved, which would explain why the disorder is severe in some collies and so mild that it causes no symptoms in another.
Diagnosis
Your veterinarian will conduct a thorough examination of the eyes to determine the extent of the defect. This can be done when your dog is still a puppy, ans is recommended. Retinal detachment is most common in the first year, and can be prevented or minimized if it is caught early on. Consult with your veterinarian about your dog’s vision. If the disease is diagnosed, it will not be expected to worsen initially unless there is a coloboma -- a hole in the lens, choroid, retina, iris, or optic disc. A coloboma may be small and have very little effect on vision, or it can be a larger hole that takes away too much of the eye structure and leads to partial or full blindness, or to retinal detachment. A coloboma, if found, will need to be carefully monitored by your veterinarian. Some patients with a minor defect may develop pigment across the affected area but will appear normal. For this reason, early examination of your collie (or herd dog) in the first six to eight weeks of life is highly recommended.
Treatment
This condition cannot be reversed. However, for certain defects such as a coloboma, surgery can sometimes be employed to minimize the effects of the disorder. Laser surgery is one method your veterinarian may suggest. Cryosurgery, which utilizes extreme cold to destroy unwanted cell or tissue, is another option for preventing retinal detachment or further deterioration. In some cases, surgery may even be used to help reattach the retina.
Living and Management
If there is a coloboma, your dog should be monitored carefully during the first year of life for signs of retinal detachment; after a year, retinal detachments rarely occur.
Collie Eye Anomaly (CEA)
Degenerative Myelopathy (DM) is a progressive neurological disorder that affects the spinal cord of dogs. Dogs that have inherited two defective copies can experience a breakdown of the cells responsible for sending and receiving signals from the brain, resulting in neurological symptoms.
The disease often begins with an unsteady gait, and the dog may wobble when they attempt to walk. As the disease progresses, the dog's hind legs will weaken and eventually the dog will be unable to walk at all. Degenerative Myelopathy moves up the body, so if the disease is allowed to progress, the dog will eventually be unable to hold his bladder and will lose normal function in its front legs. Fortunately, there is no direct pain associated with Degenerative Myelopathy.
The onset of Degenerative Myelopathy generally occurs later in life starting at an average age of about 10-12 years. However, some dogs may begin experiencing symptoms much earlier. A percentage of dogs that have inherited two copies of the mutation will not experience symptoms at all. Thus, this disease is NOT completely penetrant, meaning that while a dog with the mutation can develop Degenerative Myelopathy, the disease does not affect every dog that has the genotype.
Degenerative Myelopathy (DM)
Cyclic Neutropenia (CN) is a fatal recessive stem cell disorder that affects both smooth and rough collies. Also known as Cyclic Hematopoiesis or "Gray Collie Syndrome," dogs affected by Cyclic Neutropenia appear visibly lighter than non-affected littermates - even from puppies with the Merle coloration.
Cyclic Neutropenia is a disease that affects the neutrophils of a dog. Neutrophils are a type of white blood cell, and are an integral part of the dog's immune system. Every 10-12 days, the dog will experience a dramatic drop in the number of neutrophils circulating through their blood stream, leaving them extremely susceptible to infections. The dog will often experience diarrhea, fever, joint pain, or other symptoms associated with eye, respiratory, or skin infections. Bleeding episodes can also occur. Unfortunately, most affected dogs will die as puppies. Even with the best care, most dogs will not likely live past 2-3 years of age.
Gray Collie Syndrome is an autosomal recessive mutation, meaning that a dog must have two copies of the mutation in order to display the symptoms associated with this disorder. A dog with one copy of this mutation is known as a carrier and does not exhibit any symptoms. A dog that carries the mutation can pass on either the normal or mutant allele to any offspring. If two carriers are bred with one another, there is a 25% chance per puppy born that they will develop symptoms of CN, and a 50% chance per puppy born that they will be carriers of CN.