Title:Az ABCB1/MDR1 génmutáció elterjedtsége bizonyos magyarországi kutyaállományokban
Benedekné Major, Katalin
SUMMARY Background: P-glycoprotein is a multidrug resistance (MDR) transporter, a member of the ATP binding cassette (ABC) family and is highly expressed in capillary endothelial cells in the brain. Its physiological function is to protect the body from potentially toxic compounds. In certain dog breeds a 4-bp deletion mutation of P-glycoprotein encoding ABCB1 (MDR1) gene is frequently occurring. In result of the shift in the reading frame non-functional protein forms which leads to neurological toxicity in the affected individuals after exposure to commonly used pharmaceuticals, such as ivermectin, loperamide, cyclosporine, digoxin, acepromazine and butorphanol. The spread of mutation may constantly increase due to large scale inbreeding of purebred dogs. Objectives: The aim of our study is to evaluate the prevalence of ABCB1 gene defect in Hungarian population of the relevant dog breeds, e.g. collie, Shetland sheepdog, Australian shepherd, border collie and German shepherd. Materials and Methods: Blood samples were collected from eighty-six clientowned dogs; the owners gave signed, informed consent for study enrolment. Genomic DNA was purified via spin column based method from all samples. ABCB1 mutation was determined by modified allele specific detection method via real-time PCR analysis. Results and Discussion: Four of the investigated individuals were homozygous, five of them were heterozygous for the mutant ABCB1 allele. The mutant allele was present in collie, Shetland sheepdog, Australian shepherd dogs and none of the investigated border collies and German shepherd dogs were carrying the ABCB1 mutation. Our future plan is to involve other dog breeds to further screening. In possession of this information the veterinary drug therapy in affected dogs would be considerably risk-free. It is highly important to obtain this information regarding to different dog populations, because exclusion of the dogs carrying the nt230(del4) from breeding can significantly minimize the spread of ABCB1 gene deficiency.