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. 1996 Mar;16(3):1150–1156. doi: 10.1128/mcb.16.3.1150

A highly amplified mouse gene is homologous to the human interferon-responsive Sp100 gene encoding an autoantigen associated with nuclear dots.

T Grötzinger 1, K Jensen 1, H H Guldner 1, T Sternsdorf 1, C Szostecki 1, M Schwab 1, L Savelyeva 1, B Reich 1, H Will 1
PMCID: PMC231097  PMID: 8622659

Abstract

In human cells, three proteins are currently known to colocalize in di screte nuclear domains (designated nuclear dots): Sp100, a transcription-activating protein autoantigenic primarily in patients with primary biliary cirrhosis; PML, a tumor suppressor protein involved in development of acute promyelocytic leukemia; and NDP52, a protein of unknown function. Here we report sequence similarities between the Sp100 protein and a putative protein encoded by a highly amplified mouse gene which is visible as an inherited homogeneously staining region (HSR) on chromosome 1 of some mouse populations. By in situ hybridization, the Sp100 gene was mapped to locus 2q37, the syntenic region of the HSR on mouse chromosome 1. Unlike the highly amplified mouse gene, Sp100 was found to be a single-copy gene and showed no restriction fragment length polymorphisms. Sequence similarities in the promoter regions and similar exon-intron organizations of the two genes were revealed. As for Sp100, steady-state levels of the mRNAs of the HSR-encoded genes could be greatly increased by interferon (IFN) treatment. As in human cells, IFN treatment led to an enlargement in both size and number of nuclear dots in mouse cells as visualized by immunofluorescence staining with autoimmune sera from patients with primary biliary cirrhosis. These data indicate that a gene located in the inherited HSR of mice, designated mSp100, is homologous to the human Sp100 gene, has a similar gene organization, and responds similarly to IFN treatment.

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Selected References

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  1. Agulnik S., Plass C., Traut W., Winking H. Evolution of a long-range repeat family in chromosome 1 of the genus Mus. Mamm Genome. 1993 Dec;4(12):704–710. doi: 10.1007/BF00357793. [DOI] [PubMed] [Google Scholar]
  2. Alitalo K., Schwab M., Lin C. C., Varmus H. E., Bishop J. M. Homogeneously staining chromosomal regions contain amplified copies of an abundantly expressed cellular oncogene (c-myc) in malignant neuroendocrine cells from a human colon carcinoma. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1707–1711. doi: 10.1073/pnas.80.6.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  4. Barnes W. M. PCR amplification of up to 35-kb DNA with high fidelity and high yield from lambda bacteriophage templates. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2216–2220. doi: 10.1073/pnas.91.6.2216. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Biedler J. L., Spengler B. A. Metaphase chromosome anomaly: association with drug resistance and cell-specific products. Science. 1976 Jan 16;191(4223):185–187. doi: 10.1126/science.942798. [DOI] [PubMed] [Google Scholar]
  6. Deppert W., Haug M., Steinmayer T. Modulation of p53 protein expression during cellular transformation with simian virus 40. Mol Cell Biol. 1987 Dec;7(12):4453–4463. doi: 10.1128/mcb.7.12.4453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dyck J. A., Maul G. G., Miller W. H., Jr, Chen J. D., Kakizuka A., Evans R. M. A novel macromolecular structure is a target of the promyelocyte-retinoic acid receptor oncoprotein. Cell. 1994 Jan 28;76(2):333–343. doi: 10.1016/0092-8674(94)90340-9. [DOI] [PubMed] [Google Scholar]
  8. Eckert W. A., Plass C., Weith A., Traut W., Winking H. Transcripts from amplified sequences of an inherited homogeneously staining region in chromosome 1 of the house mouse (Mus musculus). Mol Cell Biol. 1991 Apr;11(4):2229–2235. doi: 10.1128/mcb.11.4.2229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guldner H. H., Szostecki C., Grötzinger T., Will H. IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. J Immunol. 1992 Dec 15;149(12):4067–4073. [PubMed] [Google Scholar]
  10. Koken M. H., Linares-Cruz G., Quignon F., Viron A., Chelbi-Alix M. K., Sobczak-Thépot J., Juhlin L., Degos L., Calvo F., de Thé H. The PML growth-suppressor has an altered expression in human oncogenesis. Oncogene. 1995 Apr 6;10(7):1315–1324. [PubMed] [Google Scholar]
  11. Koken M. H., Puvion-Dutilleul F., Guillemin M. C., Viron A., Linares-Cruz G., Stuurman N., de Jong L., Szostecki C., Calvo F., Chomienne C. The t(15;17) translocation alters a nuclear body in a retinoic acid-reversible fashion. EMBO J. 1994 Mar 1;13(5):1073–1083. doi: 10.1002/j.1460-2075.1994.tb06356.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Korioth F., Gieffers C., Maul G. G., Frey J. Molecular characterization of NDP52, a novel protein of the nuclear domain 10, which is redistributed upon virus infection and interferon treatment. J Cell Biol. 1995 Jul;130(1):1–13. doi: 10.1083/jcb.130.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Levy D. E., Kessler D. S., Pine R., Reich N., Darnell J. E., Jr Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev. 1988 Apr;2(4):383–393. doi: 10.1101/gad.2.4.383. [DOI] [PubMed] [Google Scholar]
  14. Liu J. H., Mu Z. M., Chang K. S. PML suppresses oncogenic transformation of NIH/3T3 cells by activated neu. J Exp Med. 1995 Jun 1;181(6):1965–1973. doi: 10.1084/jem.181.6.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Looney J. E., Ma C., Leu T. H., Flintoff W. F., Troutman W. B., Hamlin J. L. The dihydrofolate reductase amplicons in different methotrexate-resistant Chinese hamster cell lines share at least a 273-kilobase core sequence, but the amplicons in some cell lines are much larger and are remarkably uniform in structure. Mol Cell Biol. 1988 Dec;8(12):5268–5279. doi: 10.1128/mcb.8.12.5268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maul G. G., Guldner H. H., Spivack J. G. Modification of discrete nuclear domains induced by herpes simplex virus type 1 immediate early gene 1 product (ICP0). J Gen Virol. 1993 Dec;74(Pt 12):2679–2690. doi: 10.1099/0022-1317-74-12-2679. [DOI] [PubMed] [Google Scholar]
  17. Mu Z. M., Chin K. V., Liu J. H., Lozano G., Chang K. S. PML, a growth suppressor disrupted in acute promyelocytic leukemia. Mol Cell Biol. 1994 Oct;14(10):6858–6867. doi: 10.1128/mcb.14.10.6858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. O'Brien S. J., Womack J. E., Lyons L. A., Moore K. J., Jenkins N. A., Copeland N. G. Anchored reference loci for comparative genome mapping in mammals. Nat Genet. 1993 Feb;3(2):103–112. doi: 10.1038/ng0293-103. [DOI] [PubMed] [Google Scholar]
  19. Purmann L., Plass C., Grüneberg M., Winking H., Traut W. A long-range repeat cluster in chromosome 1 of the house mouse, Mus musculus, and its relation to a germline homogeneously staining region. Genomics. 1992 Jan;12(1):80–88. doi: 10.1016/0888-7543(92)90410-t. [DOI] [PubMed] [Google Scholar]
  20. Puvion-Dutilleul F., Chelbi-Alix M. K., Koken M., Quignon F., Puvion E., de Thé H. Adenovirus infection induces rearrangements in the intranuclear distribution of the nuclear body-associated PML protein. Exp Cell Res. 1995 May;218(1):9–16. doi: 10.1006/excr.1995.1125. [DOI] [PubMed] [Google Scholar]
  21. Schwab M., Alitalo K., Varmus H. E., Bishop J. M., George D. A cellular oncogene (c-Ki-ras) is amplified, overexpressed, and located within karyotypic abnormalities in mouse adrenocortical tumour cells. Nature. 1983 Jun 9;303(5917):497–501. doi: 10.1038/303497a0. [DOI] [PubMed] [Google Scholar]
  22. Sternsdorf T., Guldner H. H., Szostecki C., Grötzinger T., Will H. Two nuclear dot-associated proteins, PML and Sp100, are often co-autoimmunogenic in patients with primary biliary cirrhosis. Scand J Immunol. 1995 Aug;42(2):257–268. doi: 10.1111/j.1365-3083.1995.tb03652.x. [DOI] [PubMed] [Google Scholar]
  23. Szostecki C., Guldner H. H., Netter H. J., Will H. Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. J Immunol. 1990 Dec 15;145(12):4338–4347. [PubMed] [Google Scholar]
  24. Szostecki C., Krippner H., Penner E., Bautz F. A. Autoimmune sera recognize a 100 kD nuclear protein antigen (sp-100). Clin Exp Immunol. 1987 Apr;68(1):108–116. [PMC free article] [PubMed] [Google Scholar]
  25. Szostecki C., Will H., Netter H. J., Guldner H. H. Autoantibodies to the nuclear Sp100 protein in primary biliary cirrhosis and associated diseases: epitope specificity and immunoglobulin class distribution. Scand J Immunol. 1992 Oct;36(4):555–564. doi: 10.1111/j.1365-3083.1992.tb03224.x. [DOI] [PubMed] [Google Scholar]
  26. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  27. Terris B., Baldin V., Dubois S., Degott C., Flejou J. F., Hénin D., Dejean A. PML nuclear bodies are general targets for inflammation and cell proliferation. Cancer Res. 1995 Apr 1;55(7):1590–1597. [PubMed] [Google Scholar]
  28. Traut W., Seldin M. F., Winking H. Genetic mapping and assignment of a long-range repeat cluster to band D of chromosome 1 in Mus musculus and M. spretus. Cytogenet Cell Genet. 1992;60(2):128–130. doi: 10.1159/000133321. [DOI] [PubMed] [Google Scholar]
  29. Traut W., Winking H., Adolph S. An extra segment in chromosome 1 of wild Mus musculus: a C-band positive homogeneously staining region. Cytogenet Cell Genet. 1984;38(4):290–297. doi: 10.1159/000132077. [DOI] [PubMed] [Google Scholar]
  30. Tso J. Y., Sun X. H., Kao T. H., Reece K. S., Wu R. Isolation and characterization of rat and human glyceraldehyde-3-phosphate dehydrogenase cDNAs: genomic complexity and molecular evolution of the gene. Nucleic Acids Res. 1985 Apr 11;13(7):2485–2502. doi: 10.1093/nar/13.7.2485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Weichenhan D., Kunze B., Plass C., Hellwig T., Winking H., Traut W. A transcript family from a long-range repeat cluster of the house mouse. Genome. 1995 Apr;38(2):239–245. doi: 10.1139/g95-029. [DOI] [PubMed] [Google Scholar]
  32. Weis K., Rambaud S., Lavau C., Jansen J., Carvalho T., Carmo-Fonseca M., Lamond A., Dejean A. Retinoic acid regulates aberrant nuclear localization of PML-RAR alpha in acute promyelocytic leukemia cells. Cell. 1994 Jan 28;76(2):345–356. doi: 10.1016/0092-8674(94)90341-7. [DOI] [PubMed] [Google Scholar]
  33. Winking H., Weith A., Boldyreff B., Moriwaki K., Fredga K., Traut W. Polymorphic HSRs in chromosome 1 of the two semispecies Mus musculus musculus and M. m. domesticus have a common origin in an ancestral population. Chromosoma. 1991 Mar;100(3):147–151. doi: 10.1007/BF00337242. [DOI] [PubMed] [Google Scholar]
  34. Xie K., Lambie E. J., Snyder M. Nuclear dot antigens may specify transcriptional domains in the nucleus. Mol Cell Biol. 1993 Oct;13(10):6170–6179. doi: 10.1128/mcb.13.10.6170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de Bruijn M. H., Van der Bliek A. M., Biedler J. L., Borst P. Differential amplification and disproportionate expression of five genes in three multidrug-resistant Chinese hamster lung cell lines. Mol Cell Biol. 1986 Dec;6(12):4717–4722. doi: 10.1128/mcb.6.12.4717. [DOI] [PMC free article] [PubMed] [Google Scholar]

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