OBJECTIVE: To determine the frequency of the MDR1 gene mutation (polymorphism) associated with ivermectin sensitivity in a sample population of Collies in Washington and Idaho. ANIMALS: 40 healthy client-owned Collies. PROCEDURE: A blood sample (8 ml) was collected from each dog and used for RNA extraction. Reverse transcriptase was used to generate MDR1 cDNA. Polymerase chain reaction (PCR) primers were designed to amplify a 1,061-base pair region of the MDR1 gene. The PCR products were sequenced to determine whether the Collies had 0, 1, or 2 mutant alleles. Pedigrees of some dogs were available for analysis to determine relatedness of affected dogs. RESULTS: Of the 40 Collies, 9 (22%) were homozygous for the normal allele (normal), 17 (42%) were heterozygous (carrier), and 14 (35%) were homozygous for the mutant allele (affected). Pedigree analysis revealed that some, but not all, affected dogs were related to each other within the 4 most recent generations. CONCLUSIONS AND CLINICAL RELEVANCE: A high percentage of a sample population of Collies in Washington and Idaho are affected or carriers of the mutant MDR1 allele associated with ivermectin sensitivity. A similar frequency of this mutation may be detected in dogs from other geographic areas. Pharmacologic treatment with ivermectin, loperamide, vincristine, and other drugs that are substrates of P-glycoprotein, the MDR1 gene product, may result in neurologic toxicosis in a high percentage of Collies.
OBJECTIVE: To determine the frequency of the MDR1 gene mutation (polymorphism) associated with ivermectin sensitivity in a sample population of Collies in Washington and Idaho. ANIMALS: 40 healthy client-owned Collies. PROCEDURE: A blood sample (8 ml) was collected from each dog and used for RNA extraction. Reverse transcriptase was used to generate MDR1 cDNA. Polymerase chain reaction (PCR) primers were designed to amplify a 1,061-base pair region of the MDR1 gene. The PCR products were sequenced to determine whether the Collies had 0, 1, or 2 mutant alleles. Pedigrees of some dogs were available for analysis to determine relatedness of affected dogs. RESULTS: Of the 40 Collies, 9 (22%) were homozygous for the normal allele (normal), 17 (42%) were heterozygous (carrier), and 14 (35%) were homozygous for the mutant allele (affected). Pedigree analysis revealed that some, but not all, affected dogs were related to each other within the 4 most recent generations. CONCLUSIONS AND CLINICAL RELEVANCE: A high percentage of a sample population of Collies in Washington and Idaho are affected or carriers of the mutant MDR1 allele associated with ivermectin sensitivity. A similar frequency of this mutation may be detected in dogs from other geographic areas. Pharmacologic treatment with ivermectin, loperamide, vincristine, and other drugs that are substrates of P-glycoprotein, the MDR1 gene product, may result in neurologic toxicosis in a high percentage of Collies.
Authors: Mark W Neff; Kathryn R Robertson; Aaron K Wong; Noa Safra; Karl W Broman; Montgomery Slatkin; Katrina L Mealey; Niels C Pedersen Journal: Proc Natl Acad Sci U S A Date: 2004-08-02 Impact factor: 11.205