Cargando…

First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin

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 n...

Descripción completa

Detalles Bibliográficos
Autores principales: Nürnberger, Daniela, Müller, Simon F., Hamann, Melanie, Geyer, Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217441/
https://www.ncbi.nlm.nih.gov/pubmed/34169111
http://dx.doi.org/10.3389/fvets.2021.682393
_version_ 1783710589477978112
author Nürnberger, Daniela
Müller, Simon F.
Hamann, Melanie
Geyer, Joachim
author_facet Nürnberger, Daniela
Müller, Simon F.
Hamann, Melanie
Geyer, Joachim
author_sort Nürnberger, Daniela
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8217441
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82174412021-06-23 First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin Nürnberger, Daniela Müller, Simon F. Hamann, Melanie Geyer, Joachim Front Vet Sci Veterinary Science 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. Frontiers Media S.A. 2021-06-08 /pmc/articles/PMC8217441/ /pubmed/34169111 http://dx.doi.org/10.3389/fvets.2021.682393 Text en Copyright © 2021 Nürnberger, Müller, Hamann and Geyer. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Nürnberger, Daniela
Müller, Simon F.
Hamann, Melanie
Geyer, Joachim
First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin
title First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin
title_full First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin
title_fullStr First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin
title_full_unstemmed First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin
title_short First Sequencing of Caprine Mdr1 (Abcb1) mRNA Due to Suspected Neurological Adverse Drug Reaction in a Thuringian Goat Following Extra-Label Use of Doramectin
title_sort first sequencing of caprine mdr1 (abcb1) mrna due to suspected neurological adverse drug reaction in a thuringian goat following extra-label use of doramectin
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217441/
https://www.ncbi.nlm.nih.gov/pubmed/34169111
http://dx.doi.org/10.3389/fvets.2021.682393
work_keys_str_mv AT nurnbergerdaniela firstsequencingofcaprinemdr1abcb1mrnaduetosuspectedneurologicaladversedrugreactioninathuringiangoatfollowingextralabeluseofdoramectin
AT mullersimonf firstsequencingofcaprinemdr1abcb1mrnaduetosuspectedneurologicaladversedrugreactioninathuringiangoatfollowingextralabeluseofdoramectin
AT hamannmelanie firstsequencingofcaprinemdr1abcb1mrnaduetosuspectedneurologicaladversedrugreactioninathuringiangoatfollowingextralabeluseofdoramectin
AT geyerjoachim firstsequencingofcaprinemdr1abcb1mrnaduetosuspectedneurologicaladversedrugreactioninathuringiangoatfollowingextralabeluseofdoramectin