title: Loss of LKLF function results in embryonic lethality in mice.
abstract: Lung Kruppel-like factor (LKLF) is a member of the Kruppel-like family of zinc finger transcription factors and is closely related to erythroid kruppel-like factor (EKLF), which is necessary for beta-globin gene expression. While EKLF is expressed exclusively in erythroid cells, LKLF is expressed temporally during early embryonic development and predominantly in the adult mouse lung. To understand the role this novel transcription factor plays in development as well as tissue differentiation and function, animals lacking LKLF were produced using gene targeting technology. Mice lacking LKLF die in utero between day 11.5 and 13.5 of embryonic life and exhibit retarded growth, craniofacial abnormalities, abdominal bleeding and signs of anaemia. Although the yolk sac erythropoiesis is normal in mutant embryos, in vitro fetal liver cultures of these embryos fail to give rise to erythroid cells. Expression of other erythroid specific genes such as EKLF, GATA1 and GATA3 is unaltered in these animals. These findings demonstrate the LKLF function is indispensable during normal embryonic development, and although both LKLF and EKLF recognize common DNA motifs, they do not substitute for each other.
authors.affiliation: Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Ohio 45267-0524, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Wani
authors.forename: R T
authors.initials: RT
authors.lastname: Means
authors.forename: J B
authors.initials: JB
authors.lastname: Lingrel
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D005313:Fetal Death / Q000235:genetics* / Q000503:physiopathology*; D050982:GATA1 Transcription Factor; D050990:GATA3 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology; D051741:Kruppel-Like Transcription Factors; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D050990:GATA3 Transcription Factor; C494689:Gata1 protein, mouse; C494748:Gata3 protein, mouse; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor