GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:17318811

From GONUTS
Jump to: navigation, search
Citation

Ivanova, AV, Ivanov, SV, Pascal, V, Lumsden, JM, Ward, JM, Morris, N, Tessarolo, L, Anderson, SK and Lerman, MI (2007) Autoimmunity, spontaneous tumourigenesis, and IL-15 insufficiency in mice with a targeted disruption of the tumour suppressor gene Fus1. J. Pathol. 211:591-601

Abstract

The Fus1 gene resides in the critical 3p21.3 human chromosomal region deleted in lung and breast cancers. Recently, the tumour suppressor properties of Fus1 were confirmed experimentally by intra-tumoural administration of Fus1 that suppressed experimental lung metastasis in mice. We generated Fus1-deficient mice that were viable, fertile, and demonstrated a complex immunological phenotype. Animals with a disrupted Fus1 gene developed signs of autoimmune disease, such as vasculitis, glomerulonephritis, anaemia, circulating autoantibodies, and showed an increased frequency of spontaneous vascular tumours. Preliminary analysis of immune cell populations revealed a consistent defect in NK cell maturation in Fus1 null mice that correlated with changes in the expression of IL-15. Injection of IL-15 into Fus1 knockout mice completely rescued the NK cell maturation defect. Based on these results, we propose the hypothesis that Fus1 deficiency affects NK cell maturation through the reduction of IL-15 production but does not directly alter their developmental capacity. Since acquired immunity was not affected in Fus1-deficient animals, we suggest a relationship between the Fus1 protein and the regulation of innate immunity via IL-15 production. The increased frequency of spontaneous cancers and the development of an autoimmune syndrome in Fus1 null mice imply that these mice could serve as a model for studying molecular mechanisms of anti-tumour immunity and autoimmunity.

Links

PubMed Online version:10.1002/path.2146

Keywords

Animals; Autoimmunity/genetics; Autoimmunity/immunology; Genes, Tumor Suppressor/physiology; Hemangioma/genetics; Hemangioma/immunology; Hemangiosarcoma/genetics; Hemangiosarcoma/immunology; Immunity, Innate/immunology; Interleukin-15/immunology; Killer Cells, Natural/immunology; Mice; Mitochondria/genetics; Neoplasm Proteins/genetics; Neoplasm Proteins/immunology; Neoplasms/genetics; Neoplasms/immunology; Phenotype; Protein Precursors/analysis; Protein Precursors/deficiency; Protein Precursors/genetics; RNA, Messenger/genetics; Tissue Distribution/genetics; Tumor Suppressor Proteins; Ubiquitins/analysis; Ubiquitins/deficiency; Ubiquitins/genetics; Vasculitis/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:IL15

acts_upstream_of_or_within

GO:0032825: positive regulation of natural killer cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1931086

P

Seeded From UniProt

complete

MOUSE:IL15

acts_upstream_of_or_within

GO:0048469: cell maturation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1931086

P

  • results_in_maturation_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0001779: natural killer cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:103014

P

  • results_in_acquisition_of_features_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:TUSC2

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0048469: cell maturation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:103014

P

  • results_in_maturation_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0048469: cell maturation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:103014

P

results_in_maturation_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0032618: interleukin-15 production

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3706236

P

Seeded From UniProt

complete

MOUSE:TUSC2

part_of

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0001779: natural killer cell differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:103014

P

results_in_acquisition_of_features_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0001779: natural killer cell differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3706236

P

  • occurs_in:(EMAPA:16846)
  • results_in_acquisition_of_features_of:(CL:0000623)|occurs_in(EMAPA:32760)
  • results_in_acquisition_of_features_of:(CL:0000623)|occurs_in(EMAPA:18767)
  • results_in_acquisition_of_features_of:(CL:0000623)

Seeded From UniProt

complete

MOUSE:TUSC2

acts_upstream_of_or_within

GO:0048469: cell maturation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3706236

P

  • occurs_in:(EMAPA:18767)
  • results_in_maturation_of:(CL:0000623)|occurs_in(EMAPA:32760)
  • results_in_maturation_of:(CL:0000623)|occurs_in(EMAPA:16846)
  • results_in_maturation_of:(CL:0000623)

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.