TY - JOUR
T1 - Altered growth characteristics of skin fibroblasts from wild-derived mice, and genetic loci regulating fibroblast clone size
AU - Yuan, Rong
AU - Flurkey, Kevin
AU - Van Aelst-Bouma, Renee
AU - Zhang, Weidong
AU - King, Benjamin
AU - Austad, Steve
AU - Miller, Richard A.
AU - Harrison, David E.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/6
Y1 - 2006/6
N2 - Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1, smaller surface areas, fewer cells positive for senescence associated-β-galactosidase (SA-β-gal) and greater resistance to H2O2-induced SA-β-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 cm; Fcs2 on Chr X at 50 cm Fcs3 on Chr 4 at 51 cm and Fcs4 on Chr 10 at 25 cm. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu (GST-mu) genes are overrepresented in the 95% confidence interval of Fcs1 and Pohn TSFs have higher H2O2-induced GST-mu 4, 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.
AB - Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1, smaller surface areas, fewer cells positive for senescence associated-β-galactosidase (SA-β-gal) and greater resistance to H2O2-induced SA-β-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 cm; Fcs2 on Chr X at 50 cm Fcs3 on Chr 4 at 51 cm and Fcs4 on Chr 10 at 25 cm. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu (GST-mu) genes are overrepresented in the 95% confidence interval of Fcs1 and Pohn TSFs have higher H2O2-induced GST-mu 4, 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.
KW - Fibroblast
KW - Oxidative stress (OS)
KW - Quantitative trait locus (QTL)
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U2 - 10.1111/j.1474-9726.2006.00208.x
DO - 10.1111/j.1474-9726.2006.00208.x
M3 - Article
C2 - 16842493
AN - SCOPUS:33744477347
VL - 5
SP - 203
EP - 212
JO - Aging Cell
JF - Aging Cell
SN - 1474-9718
IS - 3
ER -