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

Xavier Cabana-Puig1, Jacob M Bond2, Zhuang Wang1

  • 1Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA.

Immunohorizons
|January 18, 2022
PubMed

Insights

MRL/lpr mice, a lupus model, show significant phenotypic drift in both colonies, impacting disease severity and organ size. Environmental factors likely contribute to these changes, necessitating strain recovery from cryopreservation.

Area of Science:

  • Immunology
  • Genetics
  • Microbiology

Background:

  • MRL/lpr mice are a common murine model for studying lupus.
  • Disease progression in these mice can vary between facilities, suggesting environmental influences.
  • A phenotypic drift was observed in an in-house colony of MRL/lpr mice.

Purpose of the Study:

  • To validate the in-house MRL/lpr mouse colony as a lupus model.
  • To compare the in-house colony with newly acquired, genetically identical mice from The Jackson Laboratory (JAX).
  • To investigate the causes of observed phenotypic differences and drift.

Main Methods:

  • Comparison of in-house MRL/lpr mice with newly obtained JAX MRL/lpr mice.
  • Assessment of phenotypic characteristics including glomerulonephritis, splenomegaly, lymphadenopathy, body weight, kidney size, splenic size, germinal center formation, and anti-dsDNA auto-IgG levels.
  • Analysis of microRNA (miR-21, miR-183) expression.
  • Characterization of gut microbiota composition.

Main Results:

  • Both in-house and new JAX mice exhibited a similar phenotypic drift, notably attenuated glomerulonephritis.
  • Differences were observed in body weight, kidney size, splenic size, germinal center formation, and anti-dsDNA auto-IgG levels between colonies (sex-specific variations noted).
  • Differential expression of miR-21 and miR-183 was observed in males, and distinct gut microbiota compositions were found at early time points.

Conclusions:

  • MRL/lpr mice display significant phenotypic drift in both JAX and in-house colonies, impacting disease characteristics.
  • Environmental factors likely play a crucial role in this drift, affecting organ size and immune markers.
  • The exact cause of attenuated glomerulonephritis remains unidentified, suggesting complex environmental interactions and the potential need for strain recovery from cryopreservation.

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