HSF1 is required for extra-embryonic development, postnatal growth and protection during inflammatory responses in mice. EMBO J 1999 Nov 01;18(21):5943-52
Date
11/02/1999Pubmed ID
10545106Pubmed Central ID
PMC1171660DOI
10.1093/emboj/18.21.5943Scopus ID
2-s2.0-0033229880 (requires institutional sign-in at Scopus site) 469 CitationsAbstract
HSF1 is the major heat shock transcriptional factor that binds heat shock element (HSE) in the promoter of heat shock proteins (Hsps) and controls rapid Hsp induction in cells subjected to various environmental stresses. Although at least four members of the vertebrate HSF family have been described, details of their individual physiological roles remain relatively obscure. To assess whether HSF1 exhibited redundant or unique in vivo functions, we created Hsf1(-/-) deficient mice. We demonstrate that homozygous Hsf1(-/-) mice can survive to adulthood but exhibit multiple phenotypes including: defects of the chorioallantoic placenta and prenatal lethality; growth retardation; female infertility; elimination of the 'classical' heat shock response; and exaggerated tumor necrosis factor alpha production resulting in increased mortality after endotoxin challenge. Because basal Hsp expression is not altered appreciably by the HSF1 null mutation, our findings suggest that this factor, like Drosophila Hsf protein, might be involved in regulating other important genes or signaling pathways. Our results establish direct causal effects for the HSF1 transactivator in regulating critical physiological events during extra-embryonic development and under pathological conditions such as sepsis to modulate pro-inflammatory responses, indicating that these pathways have clinical importance as therapeutic targets in humans.
Author List
Xiao X, Zuo X, Davis AA, McMillan DR, Curry BB, Richardson JA, Benjamin IJAuthor
Ivor J. Benjamin MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBody Weight
DNA-Binding Proteins
Disease Models, Animal
Embryonic and Fetal Development
Gene Expression Regulation
Heat Shock Transcription Factors
Heat-Shock Proteins
Inflammation
Longevity
Mice
Mice, Knockout
Phenotype
Placentation
Transcription Factors
Tumor Necrosis Factor-alpha
