Titan Mice are Unique Short-Lived Mammalian Model of Metabolic Syndrome and Aging

Peleg, S.; German Mouse Clnic (GMC),; de-Diego, I.; Sanz-Moreno, A.; Müller-Eigner, A.; Venkateswaran Venkatasubramani, A.; Langhammer, M.; Gerlini, R.; Rathkolb, B.; Aguilar-Pimentel, A.; Klein-Rodewald, T.; Calzada-Wack, J.; Becker, L.; Imhof, A.; Meng, C.; Ludwig, C.; Koch, F.; von Krusenstiern, E.; Varner, E. L.; Snyder, N. W.; Caton, V.; Brenmoehl, J.; Hoeflich, A.; Fuchs, H.; Gailus-Durner, V.; Hrabe de Angelis, M.

doi:10.1101/2020.05.11.088625

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bioRxiv · 10.1101/2020.05.11.088625

Titan Mice are Unique Short-Lived Mammalian Model of Metabolic Syndrome and Aging

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Abstract

Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The outbred mouse line Titan (DU6) results from the worlds longest selection experiment for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study deeper characterized the geno- and phenotypes of this outbred mouse line and tested its suitability as an interventional obesity model. In contrast to previous findings, our data suggests that Titan mice are metabolically unhealthy obese and short-lived. Line-specific patterns of genetic invariability are in accordance with observed phenotypic traits. Titan mice show modifications in the liver transcriptome, proteome and epigenome that are linked to metabolic (dys)regulations. However, dietary intervention partially reversed the metabolic phenotype in Titan mice and significantly extended their life expectancy. Therefore, the Titan mouse line is a valuable resource for translational and interventional obesity research.

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Peleg, S., German Mouse Clnic (GMC),, de-Diego, I., Sanz-Moreno, A., Müller-Eigner, A., Venkateswaran Venkatasubramani, A., Langhammer, M., Gerlini, R., Rathkolb, B., Aguilar-Pimentel, A., Klein-Rodewald, T., Calzada-Wack, J., Becker, L., Imhof, A., Meng, C., Ludwig, C., Koch, F., von Krusenstiern, E., Varner, E. L., Snyder, N. W., Caton, V., Brenmoehl, J., Hoeflich, A., Fuchs, H., Gailus-Durner, V., Hrabe de Angelis, M.. 2020-05-13. Titan Mice are Unique Short-Lived Mammalian Model of Metabolic Syndrome and Aging. https://doi.org/10.1101/2020.05.11.088625

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