TY - JOUR
T1 - In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene
AU - Swindell, William R.
AU - Masternak, Michal M.
AU - Bartke, Andrzej
N1 - Funding Information:
This work was supported by National Institute on Aging Grants AG023122 , AG024824 and AG198899 . W.R.S. was supported by National Institute of Health Grants T32-AG00114 and T32-AR007197 during completion of this work. We thank Lynn Winkleman and Lisa Burmeister for technical assistance related to genotyping and animal care. Dr. Richard A. Miller, Dr. Cheryl A. Conover and two anonymous reviewers provided helpful comments and critique of this manuscript.
PY - 2010/5
Y1 - 2010/5
N2 - Mice lacking the pregnancy-associated plasma protein A (PappA) gene exhibit diminished localized IGF-1 bioavailability and a 30% increase in mean life span. However, it is uncertain which tissues exhibit reduced IGF-1 signals in the PappA(-/-) mouse, and whether effects of this mutation parallel those of mutations that diminish IGF-1 in serum. Across a panel of 21 tissues, we used RT-PCR to evaluate the effects of the PappA(-/-) mutation on expression of Igfbp5, which served as an in vivo indicator of IGF-1 signaling. Among these tissues, expression of Igfbp5 was significantly reduced by PappA(-/-) only in kidney. A broader survey of IGF-associated genes in six organs identified five other genes responsive to PappA(-/-) in kidney, with stronger effects in this organ relative to other tissues. Renal expression of Irs1 and Mt1 was increased by PappA(-/-) as well as by mutations that reduce IGF-1 in serum (i.e., Ghr(-/-), Pit1(dw/. dw) and Prop1(df/. df)), and we demonstrate that expression of these genes is regulated by growth hormone-treatment and calorie restriction. These results provide in vivo data on an important new model of mammalian aging, and characterize both similar and contrasting expression patterns between long-lived mice with reduced local IGF-1 availability and diminished IGF-1 in serum.
AB - Mice lacking the pregnancy-associated plasma protein A (PappA) gene exhibit diminished localized IGF-1 bioavailability and a 30% increase in mean life span. However, it is uncertain which tissues exhibit reduced IGF-1 signals in the PappA(-/-) mouse, and whether effects of this mutation parallel those of mutations that diminish IGF-1 in serum. Across a panel of 21 tissues, we used RT-PCR to evaluate the effects of the PappA(-/-) mutation on expression of Igfbp5, which served as an in vivo indicator of IGF-1 signaling. Among these tissues, expression of Igfbp5 was significantly reduced by PappA(-/-) only in kidney. A broader survey of IGF-associated genes in six organs identified five other genes responsive to PappA(-/-) in kidney, with stronger effects in this organ relative to other tissues. Renal expression of Irs1 and Mt1 was increased by PappA(-/-) as well as by mutations that reduce IGF-1 in serum (i.e., Ghr(-/-), Pit1(dw/. dw) and Prop1(df/. df)), and we demonstrate that expression of these genes is regulated by growth hormone-treatment and calorie restriction. These results provide in vivo data on an important new model of mammalian aging, and characterize both similar and contrasting expression patterns between long-lived mice with reduced local IGF-1 availability and diminished IGF-1 in serum.
KW - Aging
KW - Dwarf
KW - Growth hormone
KW - Insulin-like growth factor
KW - Lifespan
KW - Longevity
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U2 - 10.1016/j.exger.2010.02.009
DO - 10.1016/j.exger.2010.02.009
M3 - Article
C2 - 20197085
AN - SCOPUS:77951033595
SN - 0531-5565
VL - 45
SP - 366
EP - 374
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 5
ER -