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首页> 外文期刊>Molecular and Cellular Biology >Strain-Dependent Myeloid Hyperplasia, Growth Deficiency, and Accelerated Cell Cycle in Mice Lacking the Rb-Related p107 Gene
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Strain-Dependent Myeloid Hyperplasia, Growth Deficiency, and Accelerated Cell Cycle in Mice Lacking the Rb-Related p107 Gene

机译：缺乏Rb相关p107基因的小鼠中的应变依赖性骨髓增生，生长不足和加速的细胞周期。

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To investigate the function of the Rb-related p107gene, a null mutation in p107 was introduced into the germ line of mice and bred into a BALB/cJ genetic background. Mice lackingp107 were viable and fertile but displayed impaired growth, reaching about 50% of normal weight by 21 days of age. Mutant mice exhibited a diathetic myeloproliferative disorder characterized by ectopic myeloid hyperplasia in the spleen and liver. Embryonicp107 ?/? fibroblasts and primary myoblasts isolated from adult p107 ?/? mice displayed a striking twofold acceleration in doubling time. However, cell sort analysis indicated that the fraction of cells in G1, S, and G2 was unaltered, suggesting that the different phases of the cell cycle in p107 ?/? cells was uniformly reduced by a factor of 2. Western analysis of cyclin expression in synchronized p107 ?/? fibroblasts revealed that expression of cyclins E and A preceded that of D1. Mutant embryos expressed approximately twice the normal level of Rb, whereas p130 levels were unaltered. Lastly, mutant mice reverted to a wild-type phenotype following a single backcross with C57BL/6J mice, suggesting the existence of modifier genes that have potentially epistatic relationships with p107. Therefore, we conclude thatp107 is an important player in negatively regulating the rate of progression of the cell cycle, but in a strain-dependent manner.
机译：为了研究Rb相关的 p107 基因的功能，将 p107 的无效突变引入小鼠的种系中，并繁殖到BALB / cJ遗传背景中。缺乏 p107 的小鼠是有活力且可育的，但显示出生长受损，到21天龄时达到正常体重的约50％。突变的小鼠表现出一种糖尿病性骨髓增生性疾病，其特征是脾脏和肝脏中异位的髓样增生。从成年小鼠 p107 ？/？分离的胚胎 p107 ？/？成纤维细胞和原代成肌细胞显示出惊人的双重加速在两倍的时间。但是，细胞分类分析表明，G 1 ，S和G 2 中的细胞比例未改变，表明中细胞周期的不同阶段p107 ？/？细胞均匀减少2倍。同步分析 p107 ？/？中细胞周期蛋白表达的Western分析成纤维细胞显示，细胞周期蛋白E和A的表达先于D1。突变的胚胎表达的Rb大约是正常水平的两倍，而p130的水平没有改变。最后，与C57BL / 6J小鼠进行一次回交后，突变小鼠恢复为野生型表型，表明存在与 p107 具有潜在上位性关系的修饰基因。因此，我们得出结论， p107 是负调节细胞周期进展速度的重要参与者，但以应变依赖性方式起作用。

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