Skip to main content
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1998 Aug 15;26(16):3794–3799. doi: 10.1093/nar/26.16.3794

Divergent expression of alpha1-protease inhibitor genes in mouse and human.

J Tardiff 1, K S Krauter 1
PMCID: PMC147770  PMID: 9685498

Abstract

The alpha1-protease inhibitor proteins of laboratory mice are homologous in sequence and function to human alpha1-antitrypsin and are encoded by a highly conserved multigene family comprised of five members. In humans, the inhibitor is expressed in liver and in macrophages and decreased expression or inhibitory activity is associated with a deficiency syndrome which can result in emphysema and liver disease in affected individuals. It has been proposed that macrophage expression may be an important component of the function of human alpha1-antitrypsin. Clearly, it is desirable to develop a mouse model of this deficiency syndrome, however, efforts to do this have been largely unsuccessful. In this paper, we report that aside from the issues of potentially redundant gene function, the mouse may not be a suitable animal for such studies, because there is no significant expression of murine alpha1-protease inhibitor in the macrophages of mice. This difference between the species appears to result from an absence of a functional macrophage-specific promoter in mice.

Full Text

The Full Text of this article is available as a PDF (215.6 KB).

Selected References

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

  1. Borriello F., Krauter K. S. Multiple murine alpha 1-protease inhibitor genes show unusual evolutionary divergence. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9417–9421. doi: 10.1073/pnas.88.21.9417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borriello F., Krauter K. S. Reactive site polymorphism in the murine protease inhibitor gene family is delineated using a modification of the PCR reaction (PCR + 1). Nucleic Acids Res. 1990 Sep 25;18(18):5481–5487. doi: 10.1093/nar/18.18.5481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cox D. W., Levison H. Emphysema of early onset associated with a complete deficiency of alpha-1-antitrypsin (null homozygotes). Am Rev Respir Dis. 1988 Feb;137(2):371–375. doi: 10.1164/ajrccm/137.2.371. [DOI] [PubMed] [Google Scholar]
  4. De Simone V., Ciliberto G., Hardon E., Paonessa G., Palla F., Lundberg L., Cortese R. Cis- and trans-acting elements responsible for the cell-specific expression of the human alpha 1-antitrypsin gene. EMBO J. 1987 Sep;6(9):2759–2766. doi: 10.1002/j.1460-2075.1987.tb02570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  6. Frohman M. A., Dush M. K., Martin G. R. Rapid production of full-length cDNAs from rare transcripts: amplification using a single gene-specific oligonucleotide primer. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8998–9002. doi: 10.1073/pnas.85.23.8998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grayson D. R., Costa R. H., Xanthopoulos K. G., Darnell J. E. One factor recognizes the liver-specific enhancers in alpha 1-antitrypsin and transthyretin genes. Science. 1988 Feb 12;239(4841 Pt 1):786–788. doi: 10.1126/science.3257586. [DOI] [PubMed] [Google Scholar]
  8. Grosveld F., van Assendelft G. B., Greaves D. R., Kollias G. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 1987 Dec 24;51(6):975–985. doi: 10.1016/0092-8674(87)90584-8. [DOI] [PubMed] [Google Scholar]
  9. Kraft R., Tardiff J., Krauter K. S., Leinwand L. A. Using mini-prep plasmid DNA for sequencing double stranded templates with Sequenase. Biotechniques. 1988 Jun;6(6):544-6, 549. [PubMed] [Google Scholar]
  10. Loh E. Y., Elliott J. F., Cwirla S., Lanier L. L., Davis M. M. Polymerase chain reaction with single-sided specificity: analysis of T cell receptor delta chain. Science. 1989 Jan 13;243(4888):217–220. doi: 10.1126/science.2463672. [DOI] [PubMed] [Google Scholar]
  11. Meyuhas O., Perry R. P. Construction and identification of cDNA clones for mouse ribosomal proteins: application for the study of r-protein gene expression. Gene. 1980 Jul;10(2):113–129. doi: 10.1016/0378-1119(80)90129-8. [DOI] [PubMed] [Google Scholar]
  12. Montgomery K. T., Tardiff J., Reid L. M., Krauter K. S. Negative and positive cis-acting elements control the expression of murine alpha 1-protease inhibitor genes. Mol Cell Biol. 1990 Jun;10(6):2625–2637. doi: 10.1128/mcb.10.6.2625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Muensch H., Gaidulis L., Kueppers F., So S. Y., Escano G., Kidd V. J., Woo S. L. Complete absence of serum alpha-1-antitrypsin in conjunction with an apparently normal gene structure. Am J Hum Genet. 1986 Jun;38(6):898–907. [PMC free article] [PubMed] [Google Scholar]
  14. Perlino E., Cortese R., Ciliberto G. The human alpha 1-antitrypsin gene is transcribed from two different promoters in macrophages and hepatocytes. EMBO J. 1987 Sep;6(9):2767–2771. doi: 10.1002/j.1460-2075.1987.tb02571.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Perlmutter D. H., Cole F. S., Kilbridge P., Rossing T. H., Colten H. R. Expression of the alpha 1-proteinase inhibitor gene in human monocytes and macrophages. Proc Natl Acad Sci U S A. 1985 Feb;82(3):795–799. doi: 10.1073/pnas.82.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Perlmutter D. H., Kay R. M., Cole F. S., Rossing T. H., Van Thiel D., Colten H. R. The cellular defect in alpha 1-proteinase inhibitor (alpha 1-PI) deficiency is expressed in human monocytes and in Xenopus oocytes injected with human liver mRNA. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6918–6921. doi: 10.1073/pnas.82.20.6918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ralph P., Nakoinz I. Phagocytosis and cytolysis by a macrophage tumour and its cloned cell line. Nature. 1975 Oct 2;257(5525):393–394. doi: 10.1038/257393a0. [DOI] [PubMed] [Google Scholar]
  18. Ralph P., Prichard J., Cohn M. Reticulum cell sarcoma: an effector cell in antibody-dependent cell-mediated immunity. J Immunol. 1975 Feb;114(2 Pt 2):898–905. [PubMed] [Google Scholar]
  19. Rosenfeld M. A., Siegfried W., Yoshimura K., Yoneyama K., Fukayama M., Stier L. E., Päkkö P. K., Gilardi P., Stratford-Perricaudet L. D., Perricaudet M. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science. 1991 Apr 19;252(5004):431–434. doi: 10.1126/science.2017680. [DOI] [PubMed] [Google Scholar]
  20. Silver G., Krauter K. S. Expression of cytochromes P-450c and P-450d mRNAs in cultured rat hepatocytes. 3-Methylcholanthrene induction is regulated primarily at the post-transcriptional level. J Biol Chem. 1988 Aug 25;263(24):11802–11807. [PubMed] [Google Scholar]
  21. Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. doi: 10.1093/nar/10.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wiedemann L. M., Perry R. P. Characterization of the expressed gene and several processed pseudogenes for the mouse ribosomal protein L30 gene family. Mol Cell Biol. 1984 Nov;4(11):2518–2528. doi: 10.1128/mcb.4.11.2518. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES