Loss of LKLF function results in embryonic lethality in mice

Lung Kruppel-like factor (LKLF) is a member of the Kruppel-like family of z inc finger transcription factors and is closely related to erythroid kruppe l-like factor (EKLF), which is necessary for P-globin gene expression. Whil e EKLF is expressed exclusively in erythroid cells, LKLF is expressed tempo rally during early embryonic development and predominantly in the adult mou se lung. To understand the role this novel transcription factor plays in de velopment as well as tissue differentiation and function, animals lacking L KLF 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 gro wth, craniofacial abnormalities, abdominal bleeding and signs of anaemia. A lthough the yolk sac erythropoiesis is normal in mutant embryos, in vitro f etal 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 LK LF and EKLF recognize common DNA motifs, they do not substitute for each ot her.