Mucosal characteristics vary across developmental stages in the small intestine of C57BL/6J mice

Aims: The benefits of utilizing laboratory mice include low cost, ease of maintenance, and accessibility of molecular tools. However, the ages of experimental mice in the literature vary drastically. We hypothesized that there exists age-related variation in the murine small intestine across developmental stages.Materials and methods: Segments of small intestine were harvested from C57BL/6J mice of varying ages (E17 to 24 weeks; n = 3-4/group). Slides were analyzed for morphometric parameters, cell types, and crypt proliferation index (CPI). Secondary analysis comparing age-matched males and females (n = 4/group) was performed. Means were compared with Students t-test and variance of proportions with the Chi-squared test to a significance of p < 0.05.Key findings: There were small but significant differences including regional variation in villus height, which abolished when examining the small intestine as a whole. Sexually immature mice had increased CPI compared to mature animals. The most dramatic differences were seen in mice at weaning, which demonstrated shallower crypts, increased CPI, fewer Paneth and goblet cells, and more enterochromaffin cells. Examination of embryonic intestine revealed an underdeveloped mucosa lacking differentiated cells. There were minimal differences when comparing age-matched males and females.Significance: Small, but statistically significant differences in villus height, crypt depth, and crypt proliferation are present in mice across early developmental stages. Mice at weaning exhibit variation in crypt-villus cell composition compared to older animals, which may explain the propensity for certain intestinal conditions in the very young. Investigators studying the GI mucosa should employ consistent age-matching in order to allow direct comparison between studies.