OVERLAPPING ROLES AND ASYMMETRICAL CROSS-REGULATION OF THE USF PROTEINS IN MICE

USF1 and USF2 are ubiquitously expressed transcription factors implica ted as antagonists of the c-Myc protooncoprotein in the control of cel lular proliferation. To determine the biologic al role of the USF prot eins, mutant mice were generated by homologous recombination in embryo nic stem cells, USF1-null mice were viable and fertile, with only slig ht behavioral abnormalities, However, these mice contained elevated le vels of USF2, which may compensate fur the absence of USF1. In contras t, USF2-null mice-contained reduced levels of USF1 and displayed an ob vious growth defect: they were 20-40% smaller at birth than their wild -type or heterozygous littermates and maintained a smaller size with p roportionate features throughout postnatal development, Some of the US F-deficient mice, especially among the females, were prone to spontane ous epileptic seizures, suggesting that USF is important in normal bra in function, Among the double mutants, an embryonic lethal phenotype w as observed for mice that were homozygous for the Usf2 mutation and ei ther heterozygous or homozygous for the Usf1 mutation, demonstrating t hat the USF proteins are essential in embryonic development.