Sala-Trepat J M, Poiret M, Sellem C H, Bessada R, Erdos T, Gluecksohn-Waelsch S
Proc Natl Acad Sci U S A. 1985 Apr;82(8):2442-6. doi: 10.1073/pnas.82.8.2442.
Steady-state levels of mRNAs were determined for the serum proteins albumin, alpha-fetoprotein (AFP), and transferrin, as well as for aldolase B in livers of newborn mice homozygous for a radiation-induced lethal deletion (c14CoS) in chromosome 7. Deficiencies in synthesis and secretion of the serum proteins as well as in activities of certain liver-specific enzymes characterize these homozygotes. The results of RNA dot and gel-blot hybridizations with the respective cloned cDNA probes showed a decrease to one-fourth of aldolase B mRNA levels in homozygous mutant livers compared to normal littermates, in contrast to normal levels of mRNA sequences for the three serum proteins in the mutants. Furthermore, the mRNA sequences were shown to be present as mature mRNA molecules in both mutant and normal littermate livers. We suggest that the deficiencies of liver-specific serum proteins and those of the enzymes caused by the lethal deletions around the albino locus on chromosome 7 of the mouse are due to different causes. In the case of the liver-specific enzyme examined here--i.e., aldolase B--control at the level of transcription or of message stability is affected in the homozygous deletion mutants, whereas the deficiencies of serum proteins are not reflected on the mRNA level and owe their origin to an effect on a posttranscriptional or translational level. These results lend further support to the assumption that the deleted portion of the genome includes genes concerned with the control and regulation of liver cell differentiation.
测定了新生小鼠肝脏中血清蛋白白蛋白、甲胎蛋白（AFP）和转铁蛋白以及醛缩酶B的mRNA稳态水平，这些新生小鼠对于7号染色体上辐射诱导的致死性缺失（c14CoS）是纯合的。血清蛋白合成与分泌以及某些肝脏特异性酶活性的缺陷是这些纯合子的特征。用各自克隆的cDNA探针进行RNA斑点杂交和凝胶印迹杂交的结果显示，与正常同窝仔相比，纯合突变体肝脏中醛缩酶B mRNA水平降至四分之一，而突变体中三种血清蛋白的mRNA序列水平正常。此外，mRNA序列在突变体和正常同窝仔肝脏中均以成熟mRNA分子形式存在。我们认为，小鼠7号染色体上白化病位点周围致死性缺失导致的肝脏特异性血清蛋白和酶的缺陷是由不同原因引起的。就此处检测的肝脏特异性酶即醛缩酶B而言，纯合缺失突变体中转录水平或信息稳定性的控制受到影响，而血清蛋白的缺陷在mRNA水平上未得到体现，其根源在于转录后或翻译水平的影响。这些结果进一步支持了这样一种假设，即基因组的缺失部分包含与肝细胞分化控制和调节有关的基因。
