Genetic Approaches to Elucidating the Role of Heat Shock Factor-1 (HSF-1) in Thermotolerance of Mouse Embryos
Heat shock transcription factor HSF-1 mediates the generation of heat shock proteins in response to a variety of environmental stresses. Environmental stresses, including heat and an assortment of toxins, are known to act as teratogens. Exposure to teratogens result in the death or malformations of animals exposed prenatally. Heat shock proteins (HSPs) are highly conserved proteins produced by cells in response to such exposures and have been shown to help protect organisms, including developing embryos, from damage. One of the objectives of the Mirkes lab is to study the relation of HSP production and the teratogenic effects of hyperthermia using a mouse model.
My role involves determing genotype ratios and relative thermotolerance in a line of transgenic mice. These mice have a functional deletion in either one (heterozygous) or both (homozygous) alleles for HSF-1, a transcription factor required for inducible expression of HSP. Homozygous animals do not produce HSP in response to stress. The PCR technique is used to verify genotypes of the offspring of mice carrying the transgene. Recent evidence has shown that a disproportionate number of the homozygous mice die at mid-gestation, even though not exposed to teratogens. Future studies will involve determining genotype ratios at earlier points in gestation and assessing sensitivity to hyperthermia in mouse embryos with and without functional HSF-1. Discerning the role of heat shock proteins in the developing embryo is an important contribution to understanding the causes and prevention of birth defects.
