Dataset Information

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene.

ABSTRACT: 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.

SUBMITTER: Swindell WR

PROVIDER: S-EPMC2860881 | biostudies-other | 2010 May

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene.

Swindell William R WR Masternak Michal M MM Bartke Andrzej A

Experimental gerontology 20100301 5

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 indica ...[more]

PMID: 20197085

Similar Datasets

Project description:BACKGROUND:Long-lived strains of dwarf mice carry mutations that suppress growth hormone (GH) and insulin-like growth factor I (IGF-I) signaling. The downstream effects of these endocrine abnormalities, however, are not well understood and it is unclear how these processes interact with aging mechanisms. This study presents a comparative analysis of microarray experiments that have measured hepatic gene expression levels in long-lived strains carrying one of four mutations (Prop1(df/df), Pit1(dw/dw), Ghrhr(lit/lit), GHR-KO) and describes how the effects of these mutations relate to one another at the transcriptional level. Points of overlap with the effects of calorie restriction (CR), CR mimetic compounds, low fat diets, gender dimorphism and aging were also examined. RESULTS:All dwarf mutations had larger and more consistent effects on IGF-I expression than dietary treatments. In comparison to dwarf mutations, however, the transcriptional effects of CR (and some CR mimetics) overlapped more strongly with those of aging. Surprisingly, the Ghrhr(lit/lit) mutation had much larger effects on gene expression than the GHR-KO mutation, even though both mutations affect the same endocrine pathway. Several genes potentially regulated or co-regulated with the IGF-I transcript in liver tissue were identified, including a DNA repair gene (Snm1) that is upregulated in proportion to IGF-I inhibition. A total of 13 genes exhibiting parallel differential expression patterns among all four strains of long-lived dwarf mice were identified, in addition to 30 genes with matching differential expression patterns in multiple long-lived dwarf strains and under CR. CONCLUSION:Comparative analysis of microarray datasets can identify patterns and consistencies not discernable from any one dataset individually. This study implements new analytical approaches to provide a detailed comparison among the effects of life-extending mutations, dietary treatments, gender and aging. This comparison provides insight into a broad range of issues relevant to the study of mammalian aging. In this context, 43 longevity-associated genes are identified and individual genes with the highest level of support among all microarray experiments are highlighted. These results provide promising targets for future experimental investigation as well as potential clues for understanding the functional basis of lifespan extension in mammalian systems.

Dataset Information

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene.

Publications

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets