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Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)

The abundant and widely distributed deermice Peromyscus leucopus and P. maniculatus are important reservoirs for several different zoonotic agents in North America. For the pathogens they persistently harbor, these species are also examples of the phenomenon of infection tolerance. In the present st...

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Autores principales: Barbour, Alan G., Duong, Jonathan V., Long, Anthony D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458454/
https://www.ncbi.nlm.nih.gov/pubmed/37624016
http://dx.doi.org/10.3390/pathogens12081056
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author Barbour, Alan G.
Duong, Jonathan V.
Long, Anthony D.
author_facet Barbour, Alan G.
Duong, Jonathan V.
Long, Anthony D.
author_sort Barbour, Alan G.
collection PubMed
description The abundant and widely distributed deermice Peromyscus leucopus and P. maniculatus are important reservoirs for several different zoonotic agents in North America. For the pathogens they persistently harbor, these species are also examples of the phenomenon of infection tolerance. In the present study a prior observation of absent expression of the high-affinity Fc immunoglobulin gamma receptor I (FcγRI), or CD64, in P. leucopus was confirmed in an experimental infection with Borreliella burgdorferi, a Lyme disease agent. We demonstrate that the null phenotype is attributable to a long-standing inactivation of the Fcgr1 gene in both species by a deletion of the promoter and coding sequence for the signal peptide for FcγRI. The Fcgr1 pseudogene was also documented in the related species P. polionotus. Six other Peromyscus species, including P. californicus, have coding sequences for a full-length FcγRI, including a consensus signal peptide. An inference from reported phenotypes for null Fcgr1 mutations engineered in Mus musculus is that one consequence of pseudogenization of Fcgr1 is comparatively less inflammation during infection than in animals, including humans, with undisrupted, fully active genes.
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spelling pubmed-104584542023-08-27 Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64) Barbour, Alan G. Duong, Jonathan V. Long, Anthony D. Pathogens Article The abundant and widely distributed deermice Peromyscus leucopus and P. maniculatus are important reservoirs for several different zoonotic agents in North America. For the pathogens they persistently harbor, these species are also examples of the phenomenon of infection tolerance. In the present study a prior observation of absent expression of the high-affinity Fc immunoglobulin gamma receptor I (FcγRI), or CD64, in P. leucopus was confirmed in an experimental infection with Borreliella burgdorferi, a Lyme disease agent. We demonstrate that the null phenotype is attributable to a long-standing inactivation of the Fcgr1 gene in both species by a deletion of the promoter and coding sequence for the signal peptide for FcγRI. The Fcgr1 pseudogene was also documented in the related species P. polionotus. Six other Peromyscus species, including P. californicus, have coding sequences for a full-length FcγRI, including a consensus signal peptide. An inference from reported phenotypes for null Fcgr1 mutations engineered in Mus musculus is that one consequence of pseudogenization of Fcgr1 is comparatively less inflammation during infection than in animals, including humans, with undisrupted, fully active genes. MDPI 2023-08-18 /pmc/articles/PMC10458454/ /pubmed/37624016 http://dx.doi.org/10.3390/pathogens12081056 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Barbour, Alan G.
Duong, Jonathan V.
Long, Anthony D.
Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)
title Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)
title_full Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)
title_fullStr Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)
title_full_unstemmed Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)
title_short Lyme Disease Agent Reservoirs Peromyscus leucopus and P. maniculatus Have Natively Inactivated Genes for the High-Affinity Immunoglobulin Gamma Fc Receptor I (CD64)
title_sort lyme disease agent reservoirs peromyscus leucopus and p. maniculatus have natively inactivated genes for the high-affinity immunoglobulin gamma fc receptor i (cd64)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10458454/
https://www.ncbi.nlm.nih.gov/pubmed/37624016
http://dx.doi.org/10.3390/pathogens12081056
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