Comparative analysis of the gut microbiota composition in the Cln1R151X and Cln2R207X mouse models of Batten disease and in three wild-type mouse strains

Abstract

Accumulated evidence indicates that the gut microbiota affects brain function and may be altered in neurological diseases. In this study, we analyzed the gut microbiota in Cln1R151X and Cln2R207X mice, models of the childhood neurodegenerative disorders, infantile CLN1 and late infantile CLN2 Batten diseases. Significant alterations were found in the overall gut microbiota composition and also at the individual taxonomic ranks as compared to wild-type mice. The disease-specific alterations in the gut microbiota of Cln1R151X and Cln2R207X mice may contribute to the disease phenotypes observed in these mouse models. We also compared the gut microbiota composition of three wild-type mouse strains frequently used in transgenic studies: 129S6/SvEv, C57BL/6J and mixed 129S6/SvEv × C57BL/6J. Our results show that the gut microbiota of 129S6/SvEv and C57BL/6J mice differs remarkably, which likely contributes to the known, pronounced differences in behavior and disease susceptibility between these two wild-type mouse strains.

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Availability of data and materials

The 16S rRNA gene sequencing data were deposited into the Sequence Read Archive (SRA) of NCBI (https://www.ncbi.nlm.nih.gov/sra). The SRA accession number is PRJNA627907 for the sequencing data of Cln1R151X, Cln2R207X, C57BL/6J and mixed 129S6/SvEv × C57BL/6J wild-type mice. The sequencing data for 129S6/SvEv wild-type mice is available at the PRJNA627956 SRA accession number.

Abbreviations

CNS:

Central nervous system

OTUs:

Operational taxonomic units

WT:

Wild type

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Acknowledgements

We thank Logan Langin for maintaining our mouse colony.

Funding

This work was entirely supported by Sanford Health.

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ADK and DAP designed the study, ADK and CP performed the experiments, ADK, JZ and DAP analyzed the data and wrote the paper. All authors have read and approved the manuscript.

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Correspondence to Attila D. Kovács.

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All animal procedures were carried out according to the guidelines of the Animal Welfare Act and NIH policies, and were approved by the Sanford Research Animal Care and Use Committee.

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Communicated by Erko Stackebrandt.

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Parker, C., Zhao, J., Pearce, D.A. et al. Comparative analysis of the gut microbiota composition in the Cln1R151X and Cln2R207X mouse models of Batten disease and in three wild-type mouse strains. Arch Microbiol 203, 85–96 (2021). https://doi.org/10.1007/s00203-020-02007-6

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Keywords

  • Batten disease
  • Cln1
  • Cln2
  • Gut microbiota
  • C57BL/6J
  • 129S6/SvEv