Targeted disruption of hsp70.1 sensitizes to osmotic stress

The 70 kDa heat shock protein (Hsp70) plays a critical role in cell survival and thermotolerance in response to various stress stimuli. Two nearly identical genes, hsp7O.1 and hsp7O.3, in response to environmental stress, rapidly induce Hsp70. However, it remains unclear whether these two genes are differentially regulated by various stresses. To address the physiological role of the hsp7O.1 and hsp70.3 genes in the stress response, we generated mice that specifically lack hsp70.1. In contrast to heat shock, which rapidly induced both hsp70.1 and hsp7O.3 mRNA, osmotic stress selectively induced transcription of hsp70.1. In hsp70.1-deficient embryonic fibroblasts, osmotic stress markedly reduced cell viability. Furthermore, when osmotic stress was applied in vivo, hsp7O.1-deficient mice exhibited increased apoptosis in the renal medulla. Taken together, our results demonstrate that differential expression of hsp70 genes contributes to the stress response and that the hsp7O.1 gene plays a critical role in osmotolerance.