ANALYSIS OF THE STRUCTURE AND EXPRESSION OF THE AUGMENTOR OF LIVER-REGENERATION (ALR) GENE

Background: The gene encoding the hepatotrophic factor Augmenter of Li ver Regeneration (ALR) has recently been cloned in the rat. The availa bility of the mouse form of ALR would allow the analysis of the role o f this factor in the physiology of liver and other organs, while the i dentification of the human homolog would allow the transfer of the gre at wealth of information that has been generated in animal models to c linically oriented pilot trials, and eventually the therapeutic applic ation of this information. Materials and Methods: Standard molecular b iology 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 ami no acid sequence of the human gene product deduced. The mapping of mou se and human ALR genes on mouse and human chromosomes was then complet ed. Results: The protein coding portion of the mouse ALR gene is compr ised 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 hum an ALR genes (and protein products) were found to be highly conserved and preferentially expressed in the testis and in the liver. The ALR g ene maps to the mouse chromosome 17, in a region syntenic with human c hromosome 16, where the T/t region has also been mapped. Conclusions: ALR appears to be a protein with important physiologic properties, not exclusively limited to liver regeneration, with roles that are involv ed in the synthesis or stability of the nuclear and mitochondrial tran scripts Chat are present in actively regenerating cells, particularly the germ cells of the testes.