Teaching tolerance: New approaches to enzyme replacement therapy for Pompe disease.

Sigmodontine rodents (Cricetidae: Sigmodontinae) represent the most diverse extant mammalian subfamily in both generic and species richness. Variation in conservative organ systems, such as the stomach, can provide insight into the morphological basis of their ecological diversification. Here, we examined the gross internal anatomy of 602 stomachs representing 168 species, 74 genera, and 13 tribes-approximately 80% of the subfamily's generic diversity-using sagittal and transverse sections. We propose a refined and standardized classification of stomach morphology based on the distribution of glandular and cornified epithelia. Five principal gastric designs are recognized: equiglandular, supraglandular, subglandular, discoglandular, and diverticular. The equiglandular condition predominates, occurring in approximately 65% of genera. Most tribes are characterized by a single gastric design, whereas Akodontini and Thomasomyini each exhibit multiple configurations. Notable exceptions include Phaenomys, which departs from the typical tribal pattern, and Thomasomys, the only genus exhibiting more than one stomach configuration. Ancestral-state reconstruction supports the equiglandular condition as the primitive state for Sigmodontinae and their sister clade, Tylomyinae. Independent origins of the diverticular condition in Akodontini and Thomasomyini indicate convergence, although detailed anatomical comparisons reveal distinct structural patterns. In addition, previously overlooked features-particularly the configuration of the bordering fold and its relationship to the esophageal opening and plica angularis-provide new insight into stomach organization. Overall, sigmodontine gastric morphology is structured across multiple hierarchical levels, combining strong phylogenetic signal with repeated evolutionary innovation. These results establish a comparative framework for interpreting stomach diversity and highlight the need for integrative approaches to fully understand digestive-system evolution in rodents.