1. Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice.
- Author
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Willows JW, Alshahal Z, Story NM, Alves MJ, Vidal P, Harris H, Rodrigo R, Stanford KI, Peng J, Reifsnyder PC, Harrison DE, David Arnold W, and Townsend KL
- Subjects
- Mice, Animals, Mice, Inbred C57BL, Mice, Inbred C3H, Phenotype, Species Specificity, Mice, Inbred Strains, Mice, Inbred DBA
- Abstract
We assessed aging hallmarks in skin, muscle, and adipose in the genetically diverse HET3 mouse, and generated a broad dataset comparing these to individual animal diagnostic SNPs from the 4 founding inbred strains of the HET3 line. For middle- and old-aged HET3 mice, we provided running wheel exercise to ensure our observations were not purely representative of sedentary animals, but age-related phenotypes were not improved with running wheel activity. Adipose tissue fibrosis, peripheral neuropathy, and loss of neuromuscular junction integrity were consistent phenotypes in older-aged HET3 mice regardless of physical activity, but aspects of these phenotypes were moderated by the SNP% contributions of the founding strains for the HET3 line. Taken together, the genetic contribution of founder strain SNPs moderated age-related phenotypes in skin and muscle innervation and were dependent on biological sex and chronological age. However, there was not a single founder strain (BALB/cJ, C57BL/6J, C3H/HeJ, DBA/2J) that appeared to drive more protection or disease-risk across aging in this mouse line, but genetic diversity in general was more protective., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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