Graham C, Szpirer C, Levan G, Carper D
National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
Gene. 1991 Nov 15;107(2):259-67. doi: 10.1016/0378-1119(91)90326-7.
Although the enzyme aldose reductase (AR) is implicated in the development of tissue pathology in diabetes, the exact mechanism of this involvement remains unclear. To better understand the role that expression of the aldose reductase-encoding gene (ALR) may play in diabetic complications, we have begun to analyze the gene and its regulatory regions, and we present here the sequence of four ALR genes in the rat. The putative functional gene is 14.1 kb long, has ten exons which show perfect sequence identity to the rat lens AR RNA sequence, and nine introns with classical splice-site consensus sequences. Potential regulatory elements in the 5'-flanking region of this gene include a TATA box and two CCAAT boxes. Probing rat genomic Southern blots with a fragment from the first intron indicates that there is probably only one copy of this gene in the rat genome. The other three genes are processed pseudogenes which show approx. 90% identity to the rat lens AR RNA sequence, contain no introns, and have poly(A) regions at their 3' ends. Chromosomal localization studies show the presence of ALR genes on chromosomes 3, 4 and 6 in the rat with the putative functional gene mapped on chromosome 4.
尽管醛糖还原酶（AR）与糖尿病组织病理学的发展有关，但其具体参与机制仍不清楚。为了更好地理解醛糖还原酶编码基因（ALR）的表达在糖尿病并发症中可能发挥的作用，我们开始分析该基因及其调控区域，并在此展示大鼠中四个ALR基因的序列。推测的功能基因长14.1 kb，有十个外显子，与大鼠晶状体AR RNA序列具有完全相同的序列，还有九个内含子，具有典型的剪接位点共有序列。该基因5'侧翼区域的潜在调控元件包括一个TATA盒和两个CCAAT盒。用来自第一个内含子的片段探测大鼠基因组Southern印迹表明，大鼠基因组中可能只有该基因的一个拷贝。另外三个基因是加工假基因，与大鼠晶状体AR RNA序列显示约90%的同一性，不含内含子，并且在其3'末端有poly(A)区域。染色体定位研究表明，大鼠染色体3、4和6上存在ALR基因，推测的功能基因定位在染色体4上。
