Phenotypic Drift in Lupus-Prone MRL/lpr Mice: Potential Roles of MicroRNAs and Gut Microbiota

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dc.contributor.authorCabana-Puig, Xavieren
dc.contributor.authorBond, Jacob M.en
dc.contributor.authorWang, Zhuangen
dc.contributor.authorDai, Rujuanen
dc.contributor.authorLu, Ranen
dc.contributor.authorLin, Amyen
dc.contributor.authorOakes, Vanessaen
dc.contributor.authorRizzo, Amyen
dc.contributor.authorSwartout, Briannaen
dc.contributor.authorAbdelhamid, Leilaen
dc.contributor.authorMao, Jiangdien
dc.contributor.authorPrakash, Meetaen
dc.contributor.authorSangmeister, Constanzaen
dc.contributor.authorCheung, Nathanielen
dc.contributor.authorCowan, Catharineen
dc.contributor.authorReilly, Christopher M.en
dc.contributor.authorSun, Shaen
dc.contributor.authorAhmed, S. Ansaren
dc.contributor.authorLuo, Xin M.en
dc.date.accessioned2023-04-18T17:54:53Zen
dc.date.available2023-04-18T17:54:53Zen
dc.date.issued2022en
dc.description.abstractMRL/lpr mice have been extensively used as a murine model of lupus. Disease progression in MRL/lpr mice can differ among animal facilities, suggesting a role for environmental factors.We noted a phenotypic drift of our in-house colony, which was the progeny of mice obtained from The Jackson Laboratory (JAX; stocking number 000485), that involved attenuated glomerulonephritis, increased splenomegaly, and reduced lymphadenopathy. To validate our in-house mice as a model of lupus, we compared these mice with those newly obtained from JAX, which were confirmed to be genetically identical to our in-house mice. Surprisingly, the new JAX mice exhibited a similar phenotypic drift, most notably the attenuation of glomerulonephritis. Interestingly, our in-house colony differed from JAX mice in body weight and kidney size (both sexes), as well as in splenic size, germinal center formation, and level of anti-dsDNA auto-IgG in the circulation (male only). In addition, we noted differential expression of microRNA (miR)-21 and miR-183 that might explain the splenic differences in males. Furthermore, the composition of gut microbiota was different between in-house and new JAX mice at early time points, which might explain some of the renal differences (e.g., kidney size). However, we could not identify the reason for attenuated glomerulonephritis, a shared phenotypic drift between the two colonies. It is likely that this was due to certain changes of environmental factors present in both JAX and our facilities. Taken together, these results suggest a significant phenotypic drift in MRL/lpr mice in both colonies that may require strain recovery from cryopreservation.en
dc.description.sponsorshipThis work was supported by internal funding from Virginia-Maryland College of Veterinary Medicine and National Institutes of Health Grants AR067418 and AR073240 (X.M.L.).en
dc.description.versionPublished versionen
dc.format.extent12 pgen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.4049/immunohorizons.2100082en
dc.identifier.issue1en
dc.identifier.urihttp://hdl.handle.net/10919/114561en
dc.identifier.volume6en
dc.language.isoenen
dc.publisherAmerican Association of Immunologistsen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titlePhenotypic Drift in Lupus-Prone MRL/lpr Mice: Potential Roles of MicroRNAs and Gut Microbiotaen
dc.title.serialImmunoHorizonsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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