Other Names: Ivermectin sensitivity, MDR1 gene defect, Multidrug sensitivity, MDR1
Affected Genes: ABCB1
Inheritance: Autosomal Incomplete Dominant
Mutation: chr14:13726596-13726599 (canFam3): 4 bp deletion (del AGAT)
Common Symptoms
Multidrug resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs such as the toy Australian shepherd. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, Carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*), they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs. Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications.
*Drugs known to cause neurological signs related to the MDR1 mutation:
Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine
In addition to this list, there are many other drugs known to be removed from the central nervous system via the P-glycoprotein mechanism in humans. However, reports of neurological dysfunction related to drugs other than those listed here are scarce in dogs. Please consult your veterinarian when giving drugs to known multidrug resistance 1 carriers, affected dogs, or untested dogs of breeds commonly affected with this condition.604414Other Names: Ivermectin sensitivity, MDR1 gene defect, Multidrug sensitivity, MDR1
Affected Genes: ABCB1
Inheritance: Autosomal Incomplete Dominant
Mutation: chr14:13726596-13726599 (canFam3): 4 bp deletion (del AGAT)
Common Symptoms
Multidrug resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs such as the toy Australian shepherd. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, Carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*), they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs. Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications.
*Drugs known to cause neurological signs related to the MDR1 mutation:
Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine
In addition to this list, there are many other drugs known to be removed from the central nervous system via the P-glycoprotein mechanism in humans. However, reports of neurological dysfunction related to drugs other than those listed here are scarce in dogs. Please consult your veterinarian when giving drugs to known multidrug resistance 1 carriers, affected dogs, or untested dogs of breeds commonly affected with this condition.Other Names: Ivermectin sensitivity, MDR1 gene defect, Multidrug sensitivity, MDR1
Affected Genes: ABCB1
Inheritance: Autosomal Incomplete Dominant
Mutation: chr14:13726596-13726599 (canFam3): 4 bp deletion (del AGAT)
Common Symptoms
Multidrug resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs such as the toy Australian shepherd. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, Carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*), they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs. Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications.
*Drugs known to cause neurological signs related to the MDR1 mutation:
Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine
In addition to this list, there are many other drugs known to be removed from the central nervous system via the P-glycoprotein mechanism in humans. However, reports of neurological dysfunction related to drugs other than those listed here are scarce in dogs. Please consult your veterinarian when giving drugs to known multidrug resistance 1 carriers, affected dogs, or untested dogs of breeds commonly affected with this condition.Other Names: Ivermectin sensitivity, MDR1 gene defect, Multidrug sensitivity, MDR1
Affected Genes: ABCB1
Inheritance: Autosomal Incomplete Dominant
Mutation: chr14:13726596-13726599 (canFam3): 4 bp deletion (del AGAT)
Common Symptoms
Multidrug resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs such as the toy Australian shepherd. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body. Clinical signs are most commonly associated with distribution of the drug in the central nervous system. MDR1 is inherited in an autosomal incomplete dominant manner in dogs meaning that dogs only need to inherit one copy of the mutated gene to be at an increased risk of developing adverse reactions to certain medications. Though adverse reactions to certain drugs are most commonly seen in dogs having two copies of the mutated gene, Carrier dogs can also experience drug sensitivities and dosages need to be adjusted accordingly. Thus, dogs that have one or two copies of the mutation are considered at-risk for adverse drug reactions. If an at-risk dog is treated with one of several common drugs (see below*), they are at risk of developing neurologic symptoms that could range from tremors, excess salivation, anorexia, and blindness to coma and even death. Because of the defective ability to metabolize specific drugs, these drugs can be lethal even at low doses. The MDR1 mutation does not cause adverse effects in dogs unless the dog is exposed to these drugs. Therefore, veterinarians should be notified when a dog is at risk for multidrug resistance 1 prior to administration of any medications.
*Drugs known to cause neurological signs related to the MDR1 mutation:
Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine
In addition to this list, there are many other drugs known to be removed from the central nervous system via the P-glycoprotein mechanism in humans. However, reports of neurological dysfunction related to drugs other than those listed here are scarce in dogs. Please consult your veterinarian when giving drugs to known multidrug resistance 1 carriers, affected dogs, or untested dogs of breeds commonly affected with this condition.
Other Names: Canine degenerative myelopathy, DM
Affected Genes: SOD1
Inheritance: Autosomal Recessive With Incomplete Penetrance
Mutation: chr31:26540342 (canFam3): G>A
Common Symptoms
Degenerative Myelopathy is an inherited neurologic disorder caused by a Mutation of the SOD1 gene in dogs. This mutation is found in many breeds of dog, though it is not clear for some breeds whether all dogs carrying two copies of the mutation will develop the disease. The variable presentation between breeds suggests that there are environmental or other genetic factors responsible for modifying disease expression. The average age of onset for dogs with degenerative myelopathy is approximately nine years of age. Affected dogs usually present in adulthood with gradual muscle Atrophy and loss of coordination typically beginning in the hind limbs due to degeneration of the nerves. The condition is not typically painful for the dog, but will progress until the dog is no longer able to walk. The gait of dogs affected with degenerative myelopathy can be difficult to distinguish from the gait of dogs with hip dysplasia, arthritis of other joints of the hind limbs, or intervertebral disc disease. Late in the progression of disease, dogs may lose fecal and urinary continence and the forelimbs may be affected. Affected dogs may fully lose the ability to walk 6 months to 2 years after the onset of symptoms. Affected small breed dogs often progress more slowly than affected large breed dogs and owners may postpone euthanasia until the dog is paraplegic.
Breed-Specific Information for the Toy Australian Shepherd
The toy Australian shepherd is listed as a breed susceptible to degenerative myelopathy because of its close relatedness to the Australian shepherd, which is known to develop this disease due to Mutation of the SOD1 gene. It is unknown if the toy Australian shepherd develops degenerative myelopathy due to this mutation.
Testing Tips
Genetic testing of the SOD1 gene in toy Australian shepherds will reliably determine whether a dog is a genetic Carrier of degenerative myelopathy. Degenerative Myelopathy is inherited in an Autosomal Recessive manner in dogs meaning that they must receive two copies of the mutated gene (one from each parent) to develop the disease. In general, carrier dogs do not have features of the disease but when bred with another carrier of the same Mutation, there is a risk of having affected pups. Each pup that is born to this pairing has a 25% chance of inheriting the disease and a 50% chance of inheriting one copy and being a carrier of the SOD1 gene mutation. Reliable genetic testing is important for determining breeding practices. Because symptoms may not appear until adulthood and some at-risk/affected dogs do not develop the disease, genetic testing should be performed before breeding. Until the exact modifying environmental or genetic factor is determined, genetic testing remains the only reliable way to detect neurological disease associated with this mutation prior to death. In order to eliminate this mutation from breeding lines and to avoid the potential of producing affected pups, breeding of known carriers to each other is not recommended. Toy Australian shepherds that are not carriers of the mutation have no increased risk of having affected pups.
There may be other causes of this condition in dogs and a normal result does not exclude a different mutation in this gene or any other gene that may result in a similar genetic disease or trait.