Functional study of transcription factor KLF11 by targeted gene inactivation.
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.
Song
Chao-Zhong
CZ
Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA 98195, USA. czsong@u.washington.edu
Gavriilidis
Georgios
G
Asano
Haruhiko
H
Stamatoyannopoulos
George
G
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001772:Blood Cell Count; D001835:Body Weight / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins; D015996:Survival Rate; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; C506460:KLF11 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; D005914:Globins