Document Type
Article
Publication Date
4-1-2024
Original Citation
Willows J,
Alshahal Z,
Story N,
Alves M,
Vidal P,
Harris H,
Rodrigo R,
Stanford K,
Peng J,
Reifsnyder PC,
Harrison D,
David Arnold W,
Townsend K.
Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice. Neurobiol Aging. 2024;136:58-69.
Keywords
JMG, Mice, Animals, Mice, Inbred DBA, Mice, Inbred C57BL, Mice, Inbred C3H, Phenotype, Species Specificity, Mice, Inbred Strains
JAX Source
Neurobiol Aging. 2024;136:58-69.
ISSN
1558-1497
PMID
38325031
DOI
https://doi.org/10.1016/j.neurobiolaging.2024.01.010
Grant
a collaborative sciences award (CSA) from the American Heart Associa- tion (AHA) 18CSA34090028, NIA AG022308 to DEH,
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.
Comments
This is an open access article under the CC BY-NC-ND license