Current Research & Publications
Research into the breeds that are affected and which drugs cause
problems for dogs that have the MDR1 mutation is still in progress at
the Washington State University College of Veterinary Medicine. We are
looking at other breeds to see if they have the mutation and taking
reports by owners and veterinarians on other drugs that may cause
problems for these dogs.
We are currently seeking samples from dogs of the herding breeds
(Collies, Australian Shepherds, etc.) that have experienced unexpected
reactions to drugs when administered at normal doses.
We are also working with veterinarians in Australia and France to
determine the frequency of the mutation in herding breeds in those
countries. Results of these tests are expected this year.
We are looking ahead to three important research directions
- We’d like to expand our research to identify other dog breeds that
experience a high incidence of adverse drug reactions.
- We believe there may be other chemicals and drugs that may cause
problems through this system or similar gene mutations. We’d like to
further define which chemicals and drugs those are.
- A key problem with getting needed drugs into the brain and keeping
them there is the very system that we discovered through our study of
the MDR1 gene mutation. Could this gene or others be exploited when
needed to ensure that we can get vital chemotherapeutic drugs into the
brain and hold them there? Further studies by our research group may
answer that question and provide a less toxic, more effective way to
treat cancers or diseases of the brain.
More Information and Publications
More about the initial
discovery of the cause of ivermectin sensitivity.
Researcher explains Collies’ deadly reaction to medication. Dog Fancy, June
2002, p24.
Mutant-gene discovery could help save Collies. Dog World, May 2002, p13.
Scientific and Technical Publications
Mealey KL, Gay JM, Martin LG, Waiting DK. Comparison of the
hypothalamic-pituitary-adrenal axis in MDR1-1D and MDR1 wildtype dogs. J
Vet Emergency Crit Care 2007;17:61-66.
Mealey KL. Pharmacogenetics in Veterinary Medicine. Veterinary Clinics
of North America: Small Animal Practice 2006;36:961-973.
Henick RA, Kellum HB, Bentjen SA, Mealey KL. Digoxin and mexiletine
sensitivity in a collie with the mdr1 mutation. J Vet Int Med
2006;20:415-417.
Mealey KL. Adverse Drug Reactions in Herding Breeds. Compendium of
Continuing Education for the Practicing Veterinarian 2006;28:23-33.
Kukanich B, Lascelles BD, Aman AM, Mealey KL, Papich MG. The effects of
inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid
secretion on the oral bioavailability of methadone in dogs.
2005;28:461-466
Mealey KL, Munyard KA, Bentjen SA. Frequency of the MDR1 mutation
associated with multidrug sensitivity in a sample of herding breed dogs
living in Australia. Veterinary Parasitology, 2005;131:193-196.
Mealey KL. Therapeutic implications of the MDR1 gene. Journal of
Veterinary Pharmacology and Therapeutics, 2004;27:257-264.
Neff MW, Robertson KR, Wong A, Safra N, Broman KW, Slatkin M, Mealey KL,
Pedersen NC. Breed distribution and history of canine mdr1-1d, a
pharmacogenetic mutation that marks the emergence of breeds of the
collie lineage. Proceedings of the National Academy of Sciences, 2004;
101:11725-11730.
Hugnet C, Bentjen SA, Mealey KL. Frequency of the mutant MDR1 allele
associated with multidrug sensitivity in a sample of Collies from
France. Journal of Veterinary Pharmacology and Therapeutics,
2004;27:227-229.
Sartor LL, Bentjen SA, Trepanier L, Mealey KL. Loperamide toxicity after
therapeutic doses in a Collie with the MDR1 mutation associated with
ivermectin sensitivity. Journal of Veterinary Internal Medicine,
2004;18:117-118.
Mealey KL, Northrop NC, Bentjen SA. Increased susceptibility to
P-glycoprotein substrate chemotherapeutic agents in a Collie with the
MDR1 deletion mutation associated with ivermectin sensitivity, Journal
of the American Veterinary Medical Association, 2003;223:1453-1455.
Mealey KL, Bentjen SA. Sequence and structural analysis of the
downstream promoter of the canine mdr1 gene, Journal of Veterinary and
Comparative Oncology, 2003;1(1):30-35.
Nelson OL, Carsten E, Bentjen SA, Mealey, KL. Ivermectin toxicity in an
Australian Shepherd dog with the MDR1 mutation associated with
ivermectin sensitivity in Collies, Journal of Veterinary Internal
Medicine, 2003;17:354-356.
Mealey KL, Bentjen SA, Waiting D. Frequency of the mutant MDR1 allele
associated with ivermectin sensitivity in a sample population of Collies
from the northwestern United States. American Journal of Veterinary
Research, 2002;63:479-481.
Mealey KL, Bentjen SA, Gay J, Cantor GH. Ivermectin sensitivity in
Collies is associated with a deletion mutation of the mdr1 gene.
Pharmacogenetics, 2001;11:727-733.
Last Edited: Jun 22, 2007 5:00 PM
