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 transcripti on-activating protein autoantigenic primarily in patients with primary biliary cirrhosis; PML, a tumor suppressor protein involved in develo pment of acute promyelocytic leukemia; and NDP52, a protein of unknown function. Here we report sequence similarities between the Sp100 prot ein and a putative protein encoded by a highly amplified mouse gene wh ich 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 len gth polymorphisms. Sequence similarities in the promoter regions and s imilar exon-intron organizations of the two genes were revealed. As fo r Sp100, steady-state levels of the mRNAs of the HSR-encoded genes cou ld be greatly increased by interferon (IFN) treatment. As in human cel ls. IFN treatment led to an enlargement in both size and number of nuc lear dots in mouse cells as visualized by immunofluorescence staining with autoimmune sera from patients with primary biliary cirrhosis. The se data indicate that a gene located in the inherited HSR of mice, des ignated mSp100, is homologous to the human Sp100 gene, has a similar g ene organization, and responds similarly to IFN treatment.