Key result
Allometric models outperform misleading ratio-based heart weight normalization in >25,000 mice.
Why the study?
Heart weight is commonly normalized to body weight or tibia length assuming strict proportionality, but this assumption is rarely tested and may bias group comparisons.
Observational (n=25,327)
Yes
Answers are grounded in this paper and cite their sources.
Linear models with covariate adjustment and allometric scaling provide more robust frameworks for organ weight analysis in preclinical models compared to traditional ratio-based normalization.
Heart weight (HW) is a critical parameter in cardiology and mouse research, commonly normalized to body weight (BW) or tibia length (TL) to account for size differences. Ratio-based normalization, however, assumes strict proportionality between variables, an assumption that is rarely tested and may bias group comparisons. We analysed HW, BW, and TL measurements from over 25,000 C57BL/6N wildtype mice generated by the International Mouse Phenotyping Consortium. Sex- and age-stratified analyses were combined with simulation-based modelling to evaluate empirical scaling relationships and the statistical behaviour of ratio-based normalization. Across all age and sex groups, correlations between HW, BW, and TL were negligible to weak, indicating substantial deviations from proportionality. Simulations demonstrated that ratio-based normalization can generate misleading results, including spurious or reversed group differences, when proportionality assumptions are violated. Ratios were consistent with linear and allometric models only under strictly proportional conditions, characterized by regression lines passing through the origin. Linear models with covariate adjustment and allometric scaling provide more robust and biologically meaningful frameworks for organ weight analysis. Ratio-based normalization should be avoided unless key mathematical assumptions are met.
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Oestereicher et al. (2026) conducted an observational in Healthy wildtype mice (C57BL/6N) (n=25,327). Model-based approaches (linear and allometric scaling) vs. Ratio-based normalization was evaluated on Allometric scaling exponent (b) for body weight (p=<0.001). In over 25,000 wildtype mice, correlations between heart weight and body weight were weak, demonstrating that ratio-based normalization can generate misleading results and should be replaced by allometric models.
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