|Voss, Kenneth - Ken|
Submitted to: Toxicological Sciences
Publication Type: Abstract Only
Publication Acceptance Date: 1/30/2005
Publication Date: 3/15/2005
Citation: Stauber, A.J., Liu, J., Waalkes, M.P., Brown-Borg, H., Voss, K.A., Kopchick, J.J., Corton, J.C. 2005. Constitutive expression of peroxisome proliferator-activated receptor alpha-regulated genes in dwarf mice. Toxicological Sciences. 84(S1):119. Interpretive Summary: Abstract - no summary
Technical Abstract: Defects in growth hormone (GH) secretion or signaling in mice are associated with decreased body weights (dwarfism), increased longevity, increased resistance to stress and decreases in factors which contribute to cardiovascular disease and cancer. Peroxisome proliferators (PP) alter a subset of these changes in wild-type mice through activation of the nuclear receptor family member, PP-activated receptor alpha (PPARalpha). We tested the hypothesis that an overlap in the transcriptional programs between untreated dwarf mice and PP-treated wild-type mice underlies these similarities. Using transcript profiling, we observed a statistically significant overlap in the expression of genes differentially regulated in control Snell dwarf mice (Pit-1dw) compared to phenotypically normal heterozygote (+/dw) mice. The genes included those involved in beta- and omega-oxidation of fatty acids (Acox1, Cyp-4a10, Cyp4a14) and those involved in stress responses (the chaperonin, TCP1epsilon) and cardiovascular disease (fibrinogen). The levels of some of these gene products were also altered in other dwarf mouse models including Ames, Little and GH receptor-null mice. The constitutive increases in PPARalpha-regulated genes may be partly due to increased expression of PPARalpha mRNA and protein as observed in the livers of control Snell dwarf mice. These results indicate that some of the beneficial effects associated with the dwarf phenotype may be due to constitutive activation of PPARalpha and regulated genes.