Early body weight gain in TALLYHO/JngJ mice predicts adult diabetic phenotype, mimicking childhood obesity

Abstract Childhood obesity and type 2 diabetes are two emerging health issues worldwide. To analyze their underlying causes and develop prevention strategies, mouse models are urgently needed. We present novel insights into the polygenic TALLYHO/JngJ mouse model for diabetes. By precisely analyzing our original phenotypic data, we discovered that body weight at weaning age is the main predictor of the adult phenotype in TALLYHO/JngJ mice. The higher the weaning weight of male mice, the more likely they are to develop diabetes later in life. In contrast, a low weaning weight protected against the development of the diabetic phenotype in adults. In females, we found that high weaning body weights led to a constant higher body weight throughout life. We also showed that specifically the suckling period, rather than the in utero period, is crucial for the development of the metabolic phenotype in later life. We observed an earlier onset of diabetes when the mice had higher body weights at weaning, aligning with metabolic histories observed in humans. Therefore, we recommend TALLYHO/JngJ mice as a model to investigate childhood obesity and to develop prevention strategies. Highlights The polygenic TALLYHO/JngJ mouse model is used to investigate type 2 diabetes, but the penetrance of the phenotype is highly variable. We deeply analyzed our phenotype data and find that body weight at the age of weaning (BWW) is the main predictor for the obese and diabetic phenotype in TALLYHO/JngJ male mice later in life. We suggest that TALLYHO/JngJ male mice are an excellent and urgently needed model to study childhood obesity. Our data help the relevant scientific community to better control the penetrance of the diabetic phenotype in male TALLYHO/JngJ mice. Footnotes The authors have declared that no conflict of interest exists.