TY - JOUR
T1 - Contributions of mouse genetic strain background to age-related phenotypes in physically active HET3 mice
AU - Willows, Jake W.
AU - Alshahal, Zahra
AU - Story, Naeemah M.
AU - Alves, Michele J.
AU - Vidal, Pablo
AU - Harris, Hallie
AU - Rodrigo, Rochelle
AU - Stanford, Kristin I.
AU - Peng, Juan
AU - Reifsnyder, Peter C.
AU - Harrison, David E.
AU - David Arnold, W.
AU - Townsend, Kristy L.
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - Adipose
KW - Aging
KW - Exercise
KW - Founder Strain
KW - HET3
KW - Neuromuscular
KW - Peripheral Neuropathy
KW - SNP
UR - http://www.scopus.com/inward/record.url?scp=85184142499&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2024.01.010
DO - 10.1016/j.neurobiolaging.2024.01.010
M3 - Article
C2 - 38325031
AN - SCOPUS:85184142499
SN - 0197-4580
VL - 136
SP - 58
EP - 69
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -