Abstract
Background
Preterm infants are susceptible to unique pathology due to their immaturity. Mouse models are commonly used to study immature intestinal disease, including necrotizing enterocolitis (NEC). Current NEC models are performed at a variety of ages, but data directly comparing intestinal developmental stage equivalency between mice and humans are lacking.
Methods
Small intestines were harvested from C57BL/6 mice at 3–4 days intervals from birth to P28 (n = 8 at each age). Preterm human small intestine samples representing 17–23 weeks of completed gestation were obtained from the University of Pittsburgh Health Sciences Tissue Bank, and at term gestation during reanastamoses after resection for NEC (n = 4–7 at each age). Quantification of intestinal epithelial cell types and messenger RNA for marker genes were evaluated on both species.
Results
Overall, murine and human developmental trends over time are markedly similar. Murine intestine prior to P10 is most similar to human fetal intestine prior to viability. Murine intestine at P14 is most similar to human intestine at 22–23 weeks completed gestation, and P28 murine intestine is most similar to human term intestine.
Conclusion
Use of C57BL/6J mice to model the human immature intestine is reasonable, but the age of mouse chosen is a critical factor in model development.
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Acknowledgements
S.J.M. is supported by the National Institutes of Health DK097335 and the Stead Family Department of Pediatrics, Carver College of Medicine at the University of Iowa. M.G. is supported by K08DK101608, R03DK111473, and R01DK118568 from the National Institutes of Health, March of Dimes Foundation Grant No. 5-FY17-79, the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital, and the Department of Pediatrics at Washington University School of Medicine, St. Louis. M.R.F. is supported by R01DK095004 and a Senior Research Award from the Crohn’s and Colitis Foundation.
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A.H.S., S.R.L., M.R.F., M.G., and S.J.M. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. M.G. and S.J.M. are co-senior/corresponding authors. All authors reviewed the results and approved the final version of the manuscript. Concept and design: A.H.S., M.R.F., M.G., and S.J.M. Acquisition, analysis, and interpretation of data: A.H.S., H.G., M.N., A.N.L., Q.G., W.E.L., J.J.H., S.R.L., M.R.F., M.G., and S.J.M. conducted all experimental bench work and contributed to sample analyses. Q.G. and M.G. maintained the clinical database. Statistical analysis: A.H.S., A.N.L., Q.G., W.E.L., S.R.L., M.G., and S.J.M. Manuscript preparation, drafting, and critical revisions: A.H.S., H.G., M.N., A.N.L., Q.G., W.E.L., J.J.H., S.R.L., M.R.F., M.G., and S.J.M. prepared, drafted, and critically revised the manuscript. Study supervision: M.R.F., M.G., and S.J.M.
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Stanford, A.H., Gong, H., Noonan, M. et al. A direct comparison of mouse and human intestinal development using epithelial gene expression patterns. Pediatr Res 88, 66–76 (2020). https://doi.org/10.1038/s41390-019-0472-y
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DOI: https://doi.org/10.1038/s41390-019-0472-y
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