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PMID: 7680478 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 5 ·1993-03-01 ·Pages 1756-60

Adachi M, Watanabe-Fukunaga R, Nagata S

Abstract

The mouse lpr (lymphoproliferation) mutation carries a rearrangement in the chromosomal gene for the Fas antigen, which mediates apoptosis. Isolation and characterization of mouse Fas antigen chromosomal gene from wild-type and lpr mice indicated an insertion of an early transposable element (ETn) in intron 2 of the Fas antigen gene of lpr mice. Hybrid transcripts carrying the Fas antigen and ETn sequences were expressed in the thymus and liver of the mutant. This indicated that premature termination and aberrant splicing of the Fas antigen transcript caused by the insertion of the ETn in the intron are responsible for the lymphoproliferation and autoimmune phenotype of the mutant mouse. On the other hand, an insertion of the ETn into an intron of a mammalian expression vector dramatically but not completely reduced the expression efficiency. These findings suggest that lpr mice are able to express a very low level of the Fas antigen.

MeSH Terms
Amino Acid Sequence Animals Antigens, Surface/genetics Apoptosis Base Sequence DNA Transposable Elements Gene Expression Regulation Introns Lymphoproliferative Disorders/genetics Mice Mice, Mutant Strains Molecular Sequence Data Oligodeoxyribonucleotides/chemistry Polymerase Chain Reaction RNA Splicing RNA, Messenger/genetics Restriction Mapping Transcription, Genetic fas Receptor
Chemicals
Antigens, Surface DNA Transposable Elements Oligodeoxyribonucleotides RNA, Messenger fas Receptor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Adachi M
Osaka Bioscience Institute, Japan.
Watanabe-Fukunaga R
Nagata S
References (28)
28 references, click to expand
  1. Deletion of potentially self-reactive T cell receptor specificities in L3T4-, Lyt-2- T cells of lpr mice.
    J Exp Med. 1988 Dec 1;168(6):2221-9 PMID: 3264325
  2. Abnormal thymocyte development and production of autoreactive T cells in T cell receptor transgenic autoimmune mice.
    J Immunol. 1991 Jul 15;147(2):466-74 PMID: 1830064
  3. Early differential tissue expression of transposon-like repetitive DNA sequences of the mouse.
    Proc Natl Acad Sci U S A. 1983 Sep;80(18):5641-5 PMID: 6310586
  4. Induction of various autoantibodies by mutant gene lpr in several strains of mice.
    J Immunol. 1984 Jul;133(1):227-33 PMID: 6609979
  5. The chromosomal gene structure and two mRNAs for human granulocyte colony-stimulating factor.
    EMBO J. 1986 Mar;5(3):575-81 PMID: 2423327
  6. Isolation and characterization of the cDNA for murine granulocyte colony-stimulating factor.
    Proc Natl Acad Sci U S A. 1986 Oct;83(20):7633-7 PMID: 3489940
  7. Nucleotide sequence and evolution of ETn elements.
    Proc Natl Acad Sci U S A. 1987 Jun;84(11):3768-71 PMID: 3035553
  8. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
    Anal Biochem. 1987 Apr;162(1):156-9 PMID: 2440339
  9. The developmental biology of T lymphocytes.
    Annu Rev Immunol. 1988;6:309-26 PMID: 3289569
  10. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.
    J Exp Med. 1989 May 1;169(5):1747-56 PMID: 2469768
  11. Mouse embryonic stem cells and reporter constructs to detect developmentally regulated genes.
    Science. 1989 Apr 28;244(4903):463-5 PMID: 2497519
  12. Tolerance-related V beta clonal deletions in normal CD4-8-, TCR-alpha/beta + and abnormal lpr and gld cell populations.
    J Exp Med. 1989 Dec 1;170(6):1869-77 PMID: 2511266
  13. A new allele of the lpr locus, lprcg, that complements the gld gene in induction of lymphadenopathy in the mouse.
    J Exp Med. 1990 Feb 1;171(2):519-31 PMID: 2406366
  14. Cloning of the T gene required in mesoderm formation in the mouse.
    Nature. 1990 Feb 15;343(6259):617-22 PMID: 2154694
  15. Two subfamilies of murine retrotransposon ETn sequences.
    Gene. 1990 Feb 14;86(2):269-74 PMID: 2157632
  16. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis.
    Cell. 1991 Jul 26;66(2):233-43 PMID: 1713127
  17. Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice.
    Genes Dev. 1991 Sep;5(9):1513-23 PMID: 1653172
  18. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease.
    Annu Rev Immunol. 1991;9:243-69 PMID: 1910678
  19. Inactivation of muscle chloride channel by transposon insertion in myotonic mice.
    Nature. 1991 Nov 28;354(6351):304-8 PMID: 1659665
  20. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen.
    J Immunol. 1992 Feb 15;148(4):1274-9 PMID: 1371136
  21. Transgenic T cell receptor interactions in the lymphoproliferative and autoimmune syndromes of lpr and gld mutant mice.
    Eur J Immunol. 1992 Feb;22(2):499-504 PMID: 1537383
  22. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis.
    Nature. 1992 Mar 26;356(6367):314-7 PMID: 1372394
  23. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen.
    J Biol Chem. 1992 May 25;267(15):10709-15 PMID: 1375228
  24. A gene trap approach in mouse embryonic stem cells: the lacZ reported is activated by splicing, reflects endogenous gene expression, and is mutagenic in mice.
    Genes Dev. 1992 Jun;6(6):903-18 PMID: 1592261
  25. pEF-BOS, a powerful mammalian expression vector.
    Nucleic Acids Res. 1990 Sep 11;18(17):5322 PMID: 1698283
  26. Three different mRNAs encoding human granulocyte colony-stimulating factor receptor.
    Proc Natl Acad Sci U S A. 1990 Nov;87(22):8702-6 PMID: 1701053
  27. Defect in negative selection in lpr donor-derived T cells differentiating in non-lpr host thymus.
    J Exp Med. 1991 Jan 1;173(1):127-36 PMID: 1670637
  28. Isolation and characterization of the human chromosomal gene for polypeptide chain elongation factor-1 alpha.
    J Biol Chem. 1989 Apr 5;264(10):5791-8 PMID: 2564392
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.5.1756
Published
1993-03-01
Pages
1756-60
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC45958
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.90.5.1756 PMC Full Text View journal details
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