Peters L L, Turtzo L C, Birkenmeier C S, Barker J E
Jackson Laboratory, Bar Harbor, ME 04609.
Blood. 1993 Apr 15;81(8):2144-9.
Mice homozygous for the mutation normoblastosis (gene symbol nb on chromosome 8) are deficient in erythroid ankyrin (ANK-1) and have a severe hemolytic anemia throughout life. Characteristic of the disease is a dramatic decrease in the level of expression of the Ank-1 gene (chromosome 8). The other major ankyrin transcript, brain ankyrin (Ank-2 on chromosome 3) is expressed at normal levels in nb/nb mice. Surprisingly, nb/nb fetuses have normal erythrocyte counts despite the decreased levels of Ank-1 transcripts. We previously hypothesized that fetal-specific ankyrin-related proteins could exist in nb/nb fetuses to account for the lack of detrimental effects of ANK-1 deficiency. In the present report, Western and Northern blot analyses were performed on hematopoietic cells isolated from nb/nb and +/+ fetuses. An ANK-1-related protein (165 Kd) in fetal reticulocytes persisted in adult nb/nb but not in +/+ reticulocytes. An Ank-1-related transcript of 5.5 kb was found in fetal reticulocytes. This transcript appeared to be upregulated in nb/nb but not in +/+ adult reticulocytes. A fetal-specific ANK-2-related protein (155 Kd) was present in nb/nb and in +/+ fetal reticulocytes. Ank-2-related fetal liver mRNAs were present during the time the liver was actively generating erythrocytes. Neither the Ank-2-related transcripts nor the 155-Kd ANK-2-related protein were found in +/+ or mutant adult reticulocytes. The data indicate that (1) unique ankyrin-related proteins and mRNAs present in fetal erythrocytes may stabilize the ankyrin-deficient nb/nb erythrocytes and (2) adult nb/nb mice may upregulate fetal gene transcripts to compensate for the ANK-1 deficiency.
纯合子突变型成红细胞增多症（基因符号为nb，位于8号染色体上）的小鼠缺乏红细胞锚蛋白（ANK-1），并终生患有严重的溶血性贫血。该疾病的特征是Ank-1基因（位于8号染色体上）的表达水平急剧下降。另一种主要的锚蛋白转录本，脑锚蛋白（位于3号染色体上的Ank-2）在nb/nb小鼠中表达水平正常。令人惊讶的是，尽管Ank-1转录本水平降低，但nb/nb胎儿的红细胞计数正常。我们之前推测，nb/nb胎儿中可能存在胎儿特异性的锚蛋白相关蛋白，以解释ANK-1缺乏的无害影响。在本报告中，对从nb/nb和+/+胎儿分离的造血细胞进行了蛋白质免疫印迹和RNA印迹分析。胎儿网织红细胞中的一种ANK-1相关蛋白（165 Kd）在成年nb/nb小鼠的网织红细胞中持续存在，但在+/+小鼠的网织红细胞中不存在。在胎儿网织红细胞中发现了一个5.5 kb的Ank-1相关转录本。该转录本在nb/nb成年网织红细胞中似乎上调，但在+/+成年网织红细胞中未上调。一种胎儿特异性的ANK-2相关蛋白（155 Kd）存在于nb/nb和+/+胎儿的网织红细胞中。在肝脏积极生成红细胞的时期，存在Ank-2相关的胎儿肝脏mRNA。在+/+或突变型成年网织红细胞中均未发现Ank-2相关转录本或155-Kd的ANK-2相关蛋白。数据表明：（1）胎儿红细胞中存在的独特的锚蛋白相关蛋白和mRNA可能使缺乏锚蛋白的nb/nb红细胞稳定；（2）成年nb/nb小鼠可能上调胎儿基因转录本以补偿ANK-1缺乏。
