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Targeted disruption of the heat shock transcription factor ( hsf )‐2 gene results in increased embryonic lethality, neuronal defects, and reduced spermatogenesis
Author(s) -
Wang Guanghu,
Zhang Jing,
Moskophidis Demetrius,
Mivechi Nahid F.
Publication year - 2003
Publication title -
genesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.093
H-Index - 110
eISSN - 1526-968X
pISSN - 1526-954X
DOI - 10.1002/gene.10200
Subject(s) - biology , hsf1 , heat shock factor , heat shock protein , heat shock , microbiology and biotechnology , transactivation , gene expression , transcription factor , embryogenesis , andrology , embryo , gene , genetics , hsp70 , medicine
Summary: Heat shock transcription factors (Hsfs) are major transactivators of heat shock protein (Hsp) genes in the response to stress stimuli, but are also thought to be involved in embryonic development and spermatogenesis. Among the three known mammalian Hsfs, Hsf1 is recognized as the most effective transactivator of Hsps in response to thermal challenge, but the role of Hsf2 in regulation of genes under normal or increased stress conditions in vivo remains elusive. To study its physiological function in vivo, we generated mice deficient in hsf2 by gene targeting. We report here that hsf2 −/− mice exhibit multiple phenotypes, including an increased prenatal lethality occurring between mid‐gestation to birth, with fetal death probably due to central nervous system defects including collapse of the lateral ventricles and ventricular hemorrhages. Approximately 30% of hsf2 −/− animals surviving to adulthood exhibited brain abnormalities characterized by marked dilation of the third and lateral ventricles. In addition, disruption of hsf2 resulted in reduced female fertility; however, despite ubiquitous expression in the testes and markedly reduced testis size and sperm count, only a small reduction in fertility was apparent in hsf2 −/− male mice. Immunoblotting and gene expression microarray analysis of hsf2 −/− embryos did not reveal reduced Hsp expression levels, indicating that the defects observed in hsf2 −/− embryos may not result from disruption of Hsp expression. These findings suggest that hsf2 has a major function in controlling expression of genes important for embryonic development and maintenance of sperm production. genesis 36:48–61, 2003. © 2003 Wiley‐Liss, Inc.