Heat shock proteins Hsp70-1 and Hsp70-3 Are necessary and sufficient to prevent arsenite-induced dysmorphology in mouse embryos.
Heat Shock Proteins (HSPs) represent a variety of protein families that are induced by stressors such as heat and toxicants, and the induction of HSPs in the organogenesis stage rodent embryo is well established. It has been proposed that thermotolerance and chemotolerance result from expression of the HSPs. However, whether these proteins function to prevent dysmorphogenesis and which family members serve this function are unknown. Therefore, we evaluated the specific ability of stress-inducible Hsp70-1 and Hsp70-3 to prevent arsenite-induced dysmorphology in the cultured mouse embryo using gain- and loss-of-function models. Loss of HSP function was accomplished by injecting antisense oligonucleotides directed against hsp70-1 and hsp 70-3 mRNAs into the amniotic cavity of cultured Day 9 mouse embryos. Suppression of hsp70-1 and hsp70-3 expression resulted in an up to six-fold increase in the incidence of arsenite-induced neural tube defects. Gain of HSP function was accomplished by microinjecting a transgene with a constitutive promotor driving expression of the hsp70-1 coding region, and resulted in a decreased incidence of arsenite-induced neural tube defects. These results indicate that Hsp70-1 and Hsp70-3 are both necessary and sufficient for preventing arsenite-induced dysmorphology in early-somite staged mouse embryos. Mol. Reprod. Dev. 59:285-293, 2001.
Hunter
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Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
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D000014:Abnormalities, Drug-Induced; D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D002411:Cation Exchange Resins / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D066298:In Vitro Techniques; D007202:Indicators and Reagents / Q000494:pharmacology; D008055:Lipids / Q000494:pharmacology; D051379:Mice; D008845:Microinjections; D009024:Morphogenesis / Q000187:drug effects* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012319:RNA Polymerase II / Q000378:metabolism / Q000494:pharmacology; D013723:Teratogens / Q000494:pharmacology*
D018053:Arsenites; D002411:Cation Exchange Resins; D018840:HSP70 Heat-Shock Proteins; D007202:Indicators and Reagents; D008055:Lipids; C086724:Lipofectamine; D016376:Oligonucleotides, Antisense; D013723:Teratogens; D012319:RNA Polymerase II; C015001:arsenite