Sirito M, Lin Q, Deng J M, Behringer R R, Sawadogo M
Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3758-63. doi: 10.1073/pnas.95.7.3758.
USF1 and USF2 are ubiquitously expressed transcription factors implicated as antagonists of the c-Myc protooncoprotein in the control of cellular proliferation. To determine the biological role of the USF proteins, mutant mice were generated by homologous recombination in embryonic stem cells. USF1-null mice were viable and fertile, with only slight behavioral abnormalities. However, these mice contained elevated levels of USF2, which may compensate for the absence of USF1. In contrast, USF2-null mice contained reduced levels of USF1 and displayed an obvious growth defect: they were 20-40% smaller at birth than their wild-type or heterozygous littermates and maintained a smaller size with proportionate features throughout postnatal development. Some of the USF-deficient mice, especially among the females, were prone to spontaneous epileptic seizures, suggesting that USF is important in normal brain function. Among the double mutants, an embryonic lethal phenotype was observed for mice that were homozygous for the Usf2 mutation and either heterozygous or homozygous for the Usf1 mutation, demonstrating that the USF proteins are essential in embryonic development.
USF1和USF2是普遍表达的转录因子，在细胞增殖控制中作为c-Myc原癌蛋白的拮抗剂。为了确定USF蛋白的生物学作用，通过胚胎干细胞中的同源重组产生了突变小鼠。USF1基因敲除小鼠能够存活且可育，仅有轻微的行为异常。然而，这些小鼠中USF2的水平升高，这可能补偿了USF1的缺失。相比之下，USF2基因敲除小鼠中USF1的水平降低，并表现出明显的生长缺陷：它们出生时比野生型或杂合子同窝小鼠小20%-40%，并且在出生后的整个发育过程中都保持较小的体型且比例特征正常。一些USF缺陷小鼠，尤其是雌性小鼠，容易出现自发性癫痫发作，这表明USF在正常脑功能中很重要。在双突变体中，对于Usf2突变纯合且Usf1突变杂合或纯合的小鼠观察到胚胎致死表型，这表明USF蛋白在胚胎发育中至关重要。
