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. 1996 Jan;2(1):97–108.

Analysis of the structure and expression of the augmenter of liver regeneration (ALR) gene.

R Giorda 1, M Hagiya 1, T Seki 1, M Shimonishi 1, H Sakai 1, J Michaelson 1, A Francavilla 1, T E Starzl 1, M Trucco 1
PMCID: PMC2230030  PMID: 8900538

Abstract

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Copeland N. G., Gilbert D. J., Jenkins N. A., Nadeau J. H., Eppig J. T., Maltais L. J., Miller J. C., Dietrich W. F., Steen R. G., Lincoln S. E. Genome maps IV 1993. Wall chart. Science. 1993 Oct 1;262(5130):67–82. doi: 10.1126/science.8211131. [DOI] [PubMed] [Google Scholar]
  3. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dignam J. D. Preparation of extracts from higher eukaryotes. Methods Enzymol. 1990;182:194–203. doi: 10.1016/0076-6879(90)82017-v. [DOI] [PubMed] [Google Scholar]
  5. Francavilla A., Hagiya M., Porter K. A., Polimeno L., Ihara I., Starzl T. E. Augmenter of liver regeneration: its place in the universe of hepatic growth factors. Hepatology. 1994 Sep;20(3):747–757. [PubMed] [Google Scholar]
  6. Francavilla A., Ove P., Polimeno L., Coetzee M., Makowka L., Rose J., Van Thiel D. H., Starzl T. E. Extraction and partial purification of a hepatic stimulatory substance in rats, mice, and dogs. Cancer Res. 1987 Nov 1;47(21):5600–5605. [PMC free article] [PubMed] [Google Scholar]
  7. Giorda R., Weisberg E. P., Ip T. K., Trucco M. Genomic structure and strain-specific expression of the natural killer cell receptor NKR-P1. J Immunol. 1992 Sep 15;149(6):1957–1963. [PubMed] [Google Scholar]
  8. Hagiya M., Francavilla A., Polimeno L., Ihara I., Sakai H., Seki T., Shimonishi M., Porter K. A., Starzl T. E. Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8142–8146. doi: 10.1073/pnas.91.17.8142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hagiya M., Francavilla A., Polimeno L., Ihara I., Sakai H., Seki T., Shimonishi M., Porter K. A., Starzl T. E. Cloning and sequence analysis of the rat augmenter of liver regeneration (ALR) gene: expression of biologically active recombinant ALR and demonstration of tissue distribution. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3076–3076. doi: 10.1073/pnas.92.7.3076d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LaBrecque D. R., Pesch L. A. Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver. J Physiol. 1975 Jun;248(2):273–284. doi: 10.1113/jphysiol.1975.sp010973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LaBrecque D. R., Pesch L. A. Preparation and partial characterization of hepatic regenerative stimulator substance (SS) from rat liver. J Physiol. 1975 Jun;248(2):273–284. doi: 10.1113/jphysiol.1975.sp010973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mazzaferro V., Porter K. A., Scotti-Foglieni C. L., Venkataramanan R., Makowka L., Rossaro L., Francavilla A., Todo S., Van Thiel D. H., Starzl T. E. The hepatotropic influence of cyclosporine. Surgery. 1990 May;107(5):533–539. [PMC free article] [PubMed] [Google Scholar]
  13. Moshier J. A., Deutch A. H., Huang R. C. Structure and in vitro transcription of a mouse B1 cluster containing a unique B1 dimer. Gene. 1987;58(1):19–27. doi: 10.1016/0378-1119(87)90025-4. [DOI] [PubMed] [Google Scholar]
  14. Nietfeld W., el-Baradi T., Mentzel H., Pieler T., Köster M., Pöting A., Knöchel W. Second-order repeats in Xenopus laevis finger proteins. J Mol Biol. 1989 Aug 20;208(4):639–659. doi: 10.1016/0022-2836(89)90155-1. [DOI] [PubMed] [Google Scholar]
  15. Passananti C., Felsani A., Caruso M., Amati P. Mouse genes coding for "zinc-finger"-containing proteins: characterization and expression in differentiated cells. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9417–9421. doi: 10.1073/pnas.86.23.9417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pause A., Belsham G. J., Gingras A. C., Donzé O., Lin T. A., Lawrence J. C., Jr, Sonenberg N. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature. 1994 Oct 27;371(6500):762–767. doi: 10.1038/371762a0. [DOI] [PubMed] [Google Scholar]
  17. Schmidt C., Bladt F., Goedecke S., Brinkmann V., Zschiesche W., Sharpe M., Gherardi E., Birchmeier C. Scatter factor/hepatocyte growth factor is essential for liver development. Nature. 1995 Feb 23;373(6516):699–702. doi: 10.1038/373699a0. [DOI] [PubMed] [Google Scholar]
  18. Silver L. M. The peculiar journey of a selfish chromosome: mouse t haplotypes and meiotic drive. Trends Genet. 1993 Jul;9(7):250–254. doi: 10.1016/0168-9525(93)90090-5. [DOI] [PubMed] [Google Scholar]
  19. Sonnenberg E., Meyer D., Weidner K. M., Birchmeier C. Scatter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange between mesenchyme and epithelia during mouse development. J Cell Biol. 1993 Oct;123(1):223–235. doi: 10.1083/jcb.123.1.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Starzl T. E., Jones A. F., Terblanche J., Usui S., Porter K. A., Mazzoni G. Growth-stimulating factor in regenerating canine liver. Lancet. 1979 Jan 20;1(8108):127–130. doi: 10.1016/s0140-6736(79)90519-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Starzl T. E., Porter K. A., Mazzaferro V., Todo S., Fung J., Francavilla A. Hepatotrophic effects of FK506 in dogs. Transplantation. 1991 Jan;51(1):67–70. doi: 10.1097/00007890-199101000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Starzl T. E., Schreiber S. L., Albers M. W., Porter K. A., Foglieni C. S., Francavilla A. Hepatotrophic properties in dogs of human FKBP, the binding protein for FK506 and rapamycin. Transplantation. 1991 Oct;52(4):751–753. doi: 10.1097/00007890-199110000-00038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Starzl T. E., Watanabe K., Porter K. A., Putnam C. W. Effects of insulin, glucagon, and insuling/glucagon infusions on liver morphology and cell division after complete portacaval shunt in dogs. Lancet. 1976 Apr 17;1(7964):821–825. doi: 10.1016/s0140-6736(76)90477-3. [DOI] [PubMed] [Google Scholar]
  24. TEIR H., RAVANTI K. Mitotic activity and growth factors in the liver of the white rat. Exp Cell Res. 1953 Dec;5(2):500–507. doi: 10.1016/0014-4827(53)90236-5. [DOI] [PubMed] [Google Scholar]
  25. Terblanche J., Porter K. A., Starzl T. E., Moore J., Patzelt L., Hayashida N. Stimulation of hepatic regeneration after partial hepatectomy by infusion of a cytosol extract from regenerating dog liver. Surg Gynecol Obstet. 1980 Oct;151(4):538–544. [PMC free article] [PubMed] [Google Scholar]
  26. Uehara Y., Minowa O., Mori C., Shiota K., Kuno J., Noda T., Kitamura N. Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor. Nature. 1995 Feb 23;373(6516):702–705. doi: 10.1038/373702a0. [DOI] [PubMed] [Google Scholar]

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