A highly amplified mouse gene is homologous to the human interferon-responsive Sp100 gene encoding an autoantigen associated with nuclear dots.
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.
Grötzinger
T
T
Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.
Jensen
K
K
Guldner
H H
HH
Sternsdorf
T
T
Szostecki
C
C
Schwab
M
M
Savelyeva
L
L
Reich
B
B
Will
H
H
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D002871:Chromosome Banding; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005784:Gene Amplification; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D034961:Antigens, Nuclear; D001324:Autoantigens; D009687:Nuclear Proteins; C066642:SP100 protein, human; D007372:Interferons