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Multidrug Resistance (MDR1)
| Acronym: | MDR1 |
| Gene: | ABCB1 |
| Mutation: | c.228_231del |
| Inheritance: | Autosomal recessive |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Multidrug Resistance 1 is a genetic condition where an animal cannot efficiently efflux drugs and toxins from their body. MDR1 was firstly described in dogs and then later in other animals, and it is caused by a mutation within the MDR1 gene also known as the ABCB1 gene. ABCB1 encodes for a protein that acts as the multidrug efflux transporter P-glycoprotein (P-gp). Its main role is to protect the brain from potentially neurotoxic compounds while restricting the entry of drugs and toxins into the central nervous system (CNS). The condition has been described in many dog breeds with the highest prevalence in Australian Shepherd and Border Collie dogs. Affected dogs that carry a mutation in the ABCB1 gene have P-gps with a loss of function, which is associated with increased drug susceptibility and drug accumulation in the CNS. Dogs often start to show signs of neurological toxicity such as generalized tremor, epilepsy, agitation, and panting, and often required hospitalization of the dog.
Multidrug Resistance in dogs is inherited as an autosomal recessive trait meaning both mutated ABCB1 genes are required for this condition to develop. Dogs that carry only one mutated gene will not develop the condition or show signs of neurological toxicity but may act as carriers of the specific mutation and potentially pass it to their offspring. Early genetic testing can help identify carriers and help prevent the condition from developing by proper selection of future mating pairs.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
CARRIER |
Tested mutation was detected in animal with „carrier“ result. Animal tested as carrier has one wild-type and one mutation allele, it is in heterozygous state. It will not develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
** Potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Mizukami, K., Yabuki, A., Chang, H. S., Uddin, M. M., Rahman, M. M., Kushida, K., Kohyama, M., Yamato, O. (2013). High frequency of a single nucleotide substitution (c.-6-180T>G) of the canine MDR1/ABCB1 gene associated with phenobarbital-resistant idiopathic epilepsy in Border Collie dogs. Disease markers, 35(6), 669–672. https://doi.org/10.1155/2013/695918
Gaens, D., Leithäuser, C., Hamann, M., Geyer, J. (2019). Adverse Drug Reactions After Administration of Emodepside/Praziquantel (Profender®) in an MDR1-Mutant Australian Shepherd Dog: Case Report. Frontiers in veterinary science, 6, 296. https://doi.org/10.3389/fvets.2019.00296
Henik, R. A., Kellum, H. B., Bentjen, S. A., Mealey, K. L. (2006). Digoxin and mexiletine sensitivity in a Collie with the MDR1 mutation. Journal of veterinary internal medicine, 20(2), 415–417. https://doi.org/10.1892/0891-6640(2006)20[415:damsia]2.0.co;2