The search for the mdr1-1Δ mutation of the MDR1 gene in four canine breeds in Uruguay (preliminary study)

Objective. The objective of this study is to analyze the frequency of mdr1-1Δ mutation in German Shepherd, Doberman, Border Collie and Greyhound dog breeds in Uruguay. Materials and methods. A total of 95 animals from the four breeds mentioned above were studied. DNA was isolated from blood using potassium acetate with a subsequent degradation from RNA with RNAsaH. The concentration and quality of the DNA obtained was evaluated with a Nanodrop, ND-1000 spectrophotometer. To determine the presence or absence of the mdr1-1Δ mutation, DNA samples were sent to Gene Seek, Neogen Corporation of Chicago, United States, for genotyping. Results. In all 95 animals studied, the mdr1-1Δ mutation was not present. Conclusions. Based on the preliminary results obtained, other elements that may cause adverse drug reactions must be considered: unidentified mutations in other regions of the MDR1 gene; mutations in other genes involved in the transport of drugs from the same subfamily or another; mutations in enzymes involved in drug metabolism (e.g. Cytochrome P450). Moreover, especially with Border Collies and Greyhounds, it is advisable to increase the number of animals in the study. Key words: Dogs, ivermectine, P-glycoprotein (Source: CAB)

The search for the mdr1-1Δ mutation of the MDR1 gene in four canine breeds in Uruguay (preliminary study)

Objective. The objective of this study is to analyze the frequency of mdr1-1Δ mutation in German Shepherd, Doberman, Border Collie and Greyhound dog breeds in Uruguay. Materials and methods. A total of 95 animals from the four breeds mentioned above were studied. DNA was isolated from blood using potassium acetate with a subsequent degradation from RNA with RNAsaH. The concentration and quality of the DNA obtained was evaluated with a Nanodrop, ND-1000 spectrophotometer. To determine the presence or absence of the mdr1-1Δ mutation, DNA samples were sent to Gene Seek, Neogen Corporation of Chicago, United States, for genotyping. Results. In all 95 animals studied, the mdr1-1Δ mutation was not present. Conclusions. Based on the preliminary results obtained, other elements that may cause adverse drug reactions must be considered: unidentified mutations in other regions of the MDR1 gene; mutations in other genes involved in the transport of drugs from the same subfamily or another; mutations in enzymes involved in drug metabolism (e.g. Cytochrome P450). Moreover, especially with Border Collies and Greyhounds, it is advisable to increase the number of animals in the study.Objetivo. En este trabajo se realizó la búsqueda de la mutación mdr1-1Δ en caninos de las razas Ovejero Alemán, Doberman, Galgo y Border Collie de Uruguay. Materiales y métodos. Se estudió un total de 95 animales, de las cuatro razas caninas mencionadas. El ADN se aisló a partir de muestras sanguíneas empleando acetato de potasio 8M con posterior degradación de ARN con RNAsaH. Se evaluó la concentración y calidad del ADN en un espectrofotómetro Nanodrop, ND-1000. Para conocer la presencia o ausencia de la mutación mdr1-1Δ, los ADN de las muestras extraídas se enviaron a Gene Seek, (Neogen Corporation) de Chicago, Estados Unidos. Resultados. En ninguno de los 95 animales estudiados se encontró la mutación mdr1-1Δ. Conclusiones. Dados los resultados preliminares obtenidos, se deberían considerar otros elementos que puedan causar reacciones adversas a fármacos: mutaciones aun no identificadas en otras regiones del gen MDR1; mutaciones en otros genes que intervengan en el transporte de medicamentos de la misma subfamilia u otra; mutaciones en enzimas que participan en el metabolismo de los medicamentos (ej. Citocromo P450). Por otra parte, y en particular en las razas Border Collie y Galgo es aconsejable aumentar el número de animales en estudio