GROWTH AND DIFFERENTIATION PROCEEDS NORMALLY IN CELLS DEFICIENT IN THE IMMEDIATE-EARLY GENE NGFI-A

NGFI-A (also known as EGR-1, zif/268, and Krox-24) is a zinc finger tr anscription factor induced in many cell types by a variety of growth a nd differentiation stimuli, To determine if NGFI-A plays a requisite r ole in these processes, we used homologous recombination to mutate bot h alleles of NGFI-A in embryonic stem (ES) cells and examined its effe ct on growth and differentiation. We find that ES cells lacking NGFI-A exhibit similar growth rates and serum-induced gene expression profil es compared to wild-type parental cells. They are capable of different iating into neurons, cardiac myocytes, chondrocytes, and squamous epit helium, Chimeric mice were generated from targeted ES cells, and their progeny were crossed to produce homozygous mutant mice, Growth and hi stological analyses of mice lacking NGFI-A confirm the finding in ES c ells that NGFI-A is not required for many of the processes associated with its expression and suggest that the function of NGFI-A is either more subtle in vivo or masked by redundant expression provided by othe r gene family members such as NGFI-C, Krox-20, or EGR3.