Targeted disruption of the heat shock transcription factor (hsf)-2 gene results in increased embryonic lethality, neuronal defects, and reduced spermatogenesis.
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.
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia 30912, USA.
Guanghu
G
Wang
Jing
J
Zhang
Demetrius
D
Moskophidis
Nahid F
NF
Mivechi
D000818:Animals; D002490:Central Nervous System / Q000033:anatomy & histology / Q000196:embryology*; D002874:Chromosome Mapping; D017931:DNA Primers; D005260:Female; D005328:Fetal Viability / Q000235:genetics*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout / Q000196:embryology / Q000235:genetics; D015336:Molecular Probe Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000033:anatomy & histology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D017931:DNA Primers; D006360:Heat-Shock Proteins; D014157:Transcription Factors