Functional study of transcription factor KLF11 by targeted gene inactivation.

ABSTRACT

Sp1/Krüppel-like factor (KLF) family of transcription factors regulates diverse biological processes including cell growth, differentiation, and development through modulation of gene expression. This family of factors regulates transcription positively and negatively by binding to the GC and GT/CACCC boxes in the promoter through their highly conserved three zinc finger domains. Although the molecular mechanism of gene regulation by this family of proteins has been well studied, their exact role in growth and development in vivo remains largely unknown. KLF11 has been implicated in the regulation of cell growth and gene expression. To determine the physiological function of KLF11, we generated KLF11-null mice by gene-targeting technology. Homologous KLF11(-/-) mice were bred normally and were fertile. Hematopoiesis at all stages of development was normal in the KLF11(-/-) mice. There was no effect on globin gene expression. These mice lived as long as the wild-type mice without evident pathological defects. Thus, despite its cell growth inhibition and transcriptional regulation functions observed when transiently or stably expressed in cultured cells in vitro, the results from genetic knockout suggest that KLF11 is not absolutely required for hematopoiesis, growth, and development.