Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 Dec 1;164(6):2006–2017. doi: 10.1084/jem.164.6.2006

Amyloid A gene family expression in different mouse tissues

PMCID: PMC2188489  PMID: 3783088

Abstract

Serum amyloid A (SAA) is a major acute-phase reactant and apoprotein of high density lipoprotein (HDL). SAA is encoded by a family of three active genes. We examined hepatic expression and searched for extrahepatic expression of the three SAA mRNAs after injection with casein or LPS. Studies using an SAA cDNA, which detects all three SAA mRNAs, revealed that after casein injection liver SAA mRNA was elevated approximately 1,000-fold. Adrenal gland expressed SAA mRNA at a low level (0.5% of hepatic level), and was the only extrahepatic tissue with elevated SAA mRNA after casein injection. The small intestine, primarily the ileum, and the large intestine of unstimulated control animals contained 5- and 15-fold higher SAA mRNA levels than control liver. LPS also elevated liver SAA mRNA approximately 1,000-fold. However, in contrast to casein injection, every extrahepatic tissue examined expressed SAA mRNA. Lung and kidney contained 2-5% and large intestine contained nearly 10% of SAA mRNA levels found in liver RNA. SAA mRNA levels were lower in the remaining tissues and ranged from 0.1% in the brain and pancreas to 1.0% in the small intestine, with the ileum containing 50-fold more than the duodenum. Analysis of liver with SAA1, SAA2, and SAA3 mRNA-specific oligonucleotide probes revealed that SAA1 and SAA2 mRNA were elevated approximately 50-fold higher than SAA3 mRNA after casein administration. LPS, however, induced all three SAA mRNAs equally. In extrahepatic tissues, SAA1, SAA2, and SAA3 mRNAs were expressed differentially and can be grouped into three general classes: tissues expressing all three genes, tissues expressing SAA1 and SAA3, and tissues expressing predominantly or only SAA3.

Full Text

The Full Text of this article is available as a PDF (905.5 KB).

Selected References

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

  1. Amasino R. M. Acceleration of nucleic acid hybridization rate by polyethylene glycol. Anal Biochem. 1986 Feb 1;152(2):304–307. doi: 10.1016/0003-2697(86)90413-6. [DOI] [PubMed] [Google Scholar]
  2. Baumal R., Sklar S., Wilson B., Laskov R. Casein-induced murine amyloidosis: amyloidogenesis in vitro by monolayer spleen explants of casein-injected mice. Lab Invest. 1978 Dec;39(6):632–639. [PubMed] [Google Scholar]
  3. Benditt E. P., Eriksen N. Amyloid protein SAA is associated with high density lipoprotein from human serum. Proc Natl Acad Sci U S A. 1977 Sep;74(9):4025–4028. doi: 10.1073/pnas.74.9.4025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benditt E. P., Eriksen N. Chemical classes of amyloid substance. Am J Pathol. 1971 Oct;65(1):231–252. [PMC free article] [PubMed] [Google Scholar]
  5. Benditt E. P., Eriksen N., Hanson R. H. Amyloid protein SAA is an apoprotein of mouse plasma high density lipoprotein. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4092–4096. doi: 10.1073/pnas.76.8.4092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Benson M. D., Kleiner E. Synthesis and secretion of serum amyloid protein A (SAA) by hepatocytes in mice treated with casein. J Immunol. 1980 Feb;124(2):495–499. [PubMed] [Google Scholar]
  7. Benson M. D., Scheinberg M. A., Shirahama T., Cathcart E. S., Skinner M. Kinetics of serum amyloid protein A in casein-induced murine amyloidosis. J Clin Invest. 1977 Mar;59(3):412–417. doi: 10.1172/JCI108654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Berry L. J. Bacterial toxins. CRC Crit Rev Toxicol. 1977 Nov;5(3):239–318. doi: 10.3109/10408447709082601. [DOI] [PubMed] [Google Scholar]
  9. Cathala G., Savouret J. F., Mendez B., West B. L., Karin M., Martial J. A., Baxter J. D. A method for isolation of intact, translationally active ribonucleic acid. DNA. 1983;2(4):329–335. doi: 10.1089/dna.1983.2.329. [DOI] [PubMed] [Google Scholar]
  10. Cohen A. S., Gross E., Shirahama T. The light and electron microscopic autoradiographic demonstration of local amyloid formation in spleen explants. Am J Pathol. 1965 Dec;47(6):1079–1111. [PMC free article] [PubMed] [Google Scholar]
  11. Elshourbagy N. A., Boguski M. S., Liao W. S., Jefferson L. S., Gordon J. I., Taylor J. M. Expression of rat apolipoprotein A-IV and A-I genes: mRNA induction during development and in response to glucocorticoids and insulin. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8242–8246. doi: 10.1073/pnas.82.23.8242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Elshourbagy N. A., Liao W. S., Mahley R. W., Taylor J. M. Apolipoprotein E mRNA is abundant in the brain and adrenals, as well as in the liver, and is present in other peripheral tissues of rats and marmosets. Proc Natl Acad Sci U S A. 1985 Jan;82(1):203–207. doi: 10.1073/pnas.82.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoffman J. S., Benditt E. P. Changes in high density lipoprotein content following endotoxin administration in the mouse. Formation of serum amyloid protein-rich subfractions. J Biol Chem. 1982 Sep 10;257(17):10510–10517. [PubMed] [Google Scholar]
  14. Hoffman J. S., Benditt E. P. Secretion of serum amyloid protein and assembly of serum amyloid protein-rich high density lipoprotein in primary mouse hepatocyte culture. J Biol Chem. 1982 Sep 10;257(17):10518–10522. [PubMed] [Google Scholar]
  15. Hoffman J. S., Ericsson L. H., Eriksen N., Walsh K. A., Benditt E. P. Murine tissue amyloid protein AA. NH2-terminal sequence identity with only one of two serum amyloid protein (ApoSAA) gene products. J Exp Med. 1984 Feb 1;159(2):641–646. doi: 10.1084/jem.159.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kushner I. The phenomenon of the acute phase response. Ann N Y Acad Sci. 1982;389:39–48. doi: 10.1111/j.1749-6632.1982.tb22124.x. [DOI] [PubMed] [Google Scholar]
  17. Lehrach H., Diamond D., Wozney J. M., Boedtker H. RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination. Biochemistry. 1977 Oct 18;16(21):4743–4751. doi: 10.1021/bi00640a033. [DOI] [PubMed] [Google Scholar]
  18. Levin M., Franklin E. C., Frangione B., Pras M. The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. J Clin Invest. 1972 Oct;51(10):2773–2776. doi: 10.1172/JCI107098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lowell C. A., Potter D. A., Stearman R. S., Morrow J. F. Structure of the murine serum amyloid A gene family. Gene conversion. J Biol Chem. 1986 Jun 25;261(18):8442–8452. [PubMed] [Google Scholar]
  20. Lowell C. A., Stearman R. S., Morrow J. F. Transcriptional regulation of serum amyloid A gene expression. J Biol Chem. 1986 Jun 25;261(18):8453–8461. [PubMed] [Google Scholar]
  21. Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. McAdam K. P., Li J., Knowles J., Foss N. T., Dinarello C. A., Rosenwasser L. J., Selinger M. J., Kaplan M. M., Goodman R., Herbert P. N. The biology of SAA: identification of the inducer, in vitro synthesis, and heterogeneity demonstrated with monoclonal antibodies. Ann N Y Acad Sci. 1982;389:126–136. doi: 10.1111/j.1749-6632.1982.tb22131.x. [DOI] [PubMed] [Google Scholar]
  23. McAdam K. P., Sipe J. D. Murine model for human secondary amyloidosis: genetic variability of the acute-phase serum protein SAA response to endotoxins and casein. J Exp Med. 1976 Oct 1;144(4):1121–1127. doi: 10.1084/jem.144.4.1121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Meek R. L., Hoffman J. S., Benditt E. P. Amyloidogenesis. One serum amyloid A isotype is selectively removed from the circulation. J Exp Med. 1986 Mar 1;163(3):499–510. doi: 10.1084/jem.163.3.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Meinkoth J., Wahl G. Hybridization of nucleic acids immobilized on solid supports. Anal Biochem. 1984 May 1;138(2):267–284. doi: 10.1016/0003-2697(84)90808-x. [DOI] [PubMed] [Google Scholar]
  26. Miossec P., Cavender D., Ziff M. Production of interleukin 1 by human endothelial cells. J Immunol. 1986 Apr 1;136(7):2486–2491. [PubMed] [Google Scholar]
  27. Morrow J. F., Stearman R. S., Peltzman C. G., Potter D. A. Induction of hepatic synthesis of serum amyloid A protein and actin. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4718–4722. doi: 10.1073/pnas.78.8.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pepys M. B., Baltz M. L. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol. 1983;34:141–212. doi: 10.1016/s0065-2776(08)60379-x. [DOI] [PubMed] [Google Scholar]
  29. Ramadori G., Sipe J. D., Colten H. R. Expression and regulation of the murine serum amyloid A (SAA) gene in extrahepatic sites. J Immunol. 1985 Dec;135(6):3645–3647. [PubMed] [Google Scholar]
  30. Rosenstreich D. L., McAdam K. P. Lymphoid cells in endotoxin-induced production of the amyloid-related serum amyloid A protein. Infect Immun. 1979 Jan;23(1):181–183. doi: 10.1128/iai.23.1.181-183.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rosenthal C. J., Franklin E. C., Frangione B., Greenspan J. Isolation and partial characterization of SAA-an amyloid-related protein from human serum. J Immunol. 1976 May;116(5):1415–1418. [PubMed] [Google Scholar]
  32. Selinger M. J., McAdam K. P., Kaplan M. M., Sipe J. D., Vogel S. N., Rosenstreich D. L. Monokine-induced synthesis of serum amyloid A protein by hepatocytes. Nature. 1980 Jun 12;285(5765):498–500. doi: 10.1038/285498a0. [DOI] [PubMed] [Google Scholar]
  33. Sipe J. D., Colten H. R., Goldberger G., Edge M. D., Tack B. F., Cohen A. S., Whitehead A. S. Human serum amyloid A (SAA): biosynthesis and postsynthetic processing of preSAA and structural variants defined by complementary DNA. Biochemistry. 1985 Jun 4;24(12):2931–2936. doi: 10.1021/bi00333a018. [DOI] [PubMed] [Google Scholar]
  34. Sipe J. D., Vogel S. N., Ryan J. L., McAdam K. P., Rosenstreich D. L. Detection of a mediator derived from endotoxin-stimulated macrohpages that induces the acute phase serum amyloid A response in mice. J Exp Med. 1979 Sep 19;150(3):597–606. doi: 10.1084/jem.150.3.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sipe J. D., Vogel S. N., Sztein M. B., Skinner M., Cohen A. S. The role of interleukin 1 in acute phase serum amyloid A (SAA) and serum amyloid P (SAP) biosynthesis. Ann N Y Acad Sci. 1982;389:137–150. doi: 10.1111/j.1749-6632.1982.tb22132.x. [DOI] [PubMed] [Google Scholar]
  36. Stearman R. S., Lowell C. A., Peltzman C. G., Morrow J. F. The sequence and structure of a new serum amyloid A gene. Nucleic Acids Res. 1986 Jan 24;14(2):797–809. doi: 10.1093/nar/14.2.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sztein M. B., Vogel S. N., Sipe J. D., Murphy P. A., Mizel S. B., Oppenheim J. J., Rosenstreich D. L. The role of macrophages in the acute-phase response: SAA inducer is closely related to lymphocyte activating factor and endogenous pyrogen. Cell Immunol. 1981 Sep 1;63(1):164–176. doi: 10.1016/0008-8749(81)90037-x. [DOI] [PubMed] [Google Scholar]
  38. Thomas P. S. Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5201–5205. doi: 10.1073/pnas.77.9.5201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yamamoto K., Migita S. Complete primary structures of two major murine serum amyloid A proteins deduced from cDNA sequences. Proc Natl Acad Sci U S A. 1985 May;82(9):2915–2919. doi: 10.1073/pnas.82.9.2915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yamamoto K., Shiroo M., Migita S. Diverse gene expression for isotypes of murine serum amyloid A protein during acute phase reaction. Science. 1986 Apr 11;232(4747):227–229. doi: 10.1126/science.3456645. [DOI] [PubMed] [Google Scholar]
  41. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES