The multidrug resistance gene MDR1 encodes for an efflux transporter called
P-glycoprotein (P-gp). In the canine Mdr1 gene, a
nonsense mutation was identified in certain dog breeds causing increased
drug sensitivity to various P-gp substrates such as
antiparasitic macrocyclic
lactones. Symptoms of neurologic toxicity include
ataxia, depression, salivation,
tremor, apparent
blindness, and
mydriasis. In the current report, a Thuringian goat developed similar neurological signs
after treatment with
doramectin, a compound from the macrocyclic
lactone class. Therefore, Mdr1 might be defective in this individual goat. For diagnostic purposes, sequencing of the complete
mRNA transcript coding for caprine Mdr1 was performed to investigate a potential missense mutation. The Mdr1 transcripts of two related goats without
drug sensitivity were also sequenced to allow differential diagnosis and were compared to the suspected
drug-sensitive goat. The only position where the Mdr1 sequence from the suspected
drug-sensitive goat differed was in the 3'-untranslated region, being a heterozygous single nucleotide polymorphism c.3875C>A. It can be suspected that this variant affects the expression level, stability, or translation efficiency of the Mdr1
mRNA transcript and therefore might be associated with the suspected
drug sensitivity. To clarify this, further studies are needed, particularly investigating the Mdr1
mRNA and
protein expression levels from brain material of affected goats. In conclusion, Mdr1 variants may exist not only in dogs, but also in individual goats. The current report provides the first Mdr1
mRNA transcript sequence of a goat and therefore represents the basis for more detailed Mdr1 sequence and expression analyses.