Giorda R, Hagiya M, Seki T, Shimonishi M, Sakai H, Michaelson J, Francavilla A, Starzl T E, Trucco M
Department of Pediatrics, University of Pittsburgh, Pennsylvania, USA.
Mol Med. 1996 Jan;2(1):97-108.
The gene encoding the hepatotrophic factor Augmenter of Liver Regeneration (ALR) has recently been cloned in the rat. The availability of the mouse form of ALR would allow the analysis of the role of this factor in the physiology of liver and other organs, while the identification of the human homolog would allow the transfer of the great wealth of information that has been generated in animal models to clinically oriented pilot trials, and eventually the therapeutic application of this information.
Standard molecular biology approaches have been used to determine the genomic structure of the ALR gene in the mouse, and to characterize the ALR transcript and its protein product. The human ALR cDNA was also isolated and the amino acid sequence of the human gene product deduced. The mapping of mouse and human ALR genes on mouse and human chromosomes was then completed.
The protein coding portion of the mouse ALR gene is comprised of three exons, the first containing the 5' untranslated sequence and the initial 18 bases after the ATG translation initiation codon, the second exon encompasses 198 bases, and the third exon contains the remaining portion of the protein coding sequence. Rat, mouse, and human ALR genes (and protein products) were found to be highly conserved and preferentially expressed in the testis and in the liver. The ALR gene maps to the mouse chromosome 17, in a region syntenic with human chromosome 16, where the T/t region has also been mapped.
ALR appears to be a protein with important physiologic properties, not exclusively limited to liver regeneration, with roles that are involved in the synthesis or stability of the nuclear and mitochondrial transcripts that are present in actively regenerating cells, particularly the germ cells of the testes.
编码肝营养因子肝再生增强因子(ALR)的基因最近已在大鼠中克隆出来。获得小鼠形式的ALR将有助于分析该因子在肝脏和其他器官生理学中的作用,而鉴定人类同源物将有助于将在动物模型中产生的大量信息应用于以临床为导向的初步试验,并最终将这些信息用于治疗。
已使用标准分子生物学方法来确定小鼠中ALR基因的基因组结构,并对ALR转录本及其蛋白质产物进行表征。还分离了人类ALR cDNA,并推导了人类基因产物的氨基酸序列。然后完成了小鼠和人类ALR基因在小鼠和人类染色体上的定位。
小鼠ALR基因的蛋白质编码部分由三个外显子组成,第一个外显子包含5'非翻译序列和ATG翻译起始密码子后的最初18个碱基,第二个外显子包含198个碱基,第三个外显子包含蛋白质编码序列的其余部分。发现大鼠、小鼠和人类的ALR基因(及其蛋白质产物)高度保守,并在睾丸和肝脏中优先表达。ALR基因定位于小鼠第17号染色体上,该区域与人类第16号染色体同线,T/t区域也已定位在此处。
ALR似乎是一种具有重要生理特性的蛋白质,不仅限于肝再生,其作用涉及活跃再生细胞(特别是睾丸生殖细胞)中存在的核转录本和线粒体转录本的合成或稳定性。