The expression of influenza virus hemagglutinin in the pancreatic beta cells of transgenic mice results in autoimmune diabetes.
Insulin-dependent diabetes mellitus results from the autoimmune destruction of the insulin-producing beta cells of the pancreatic islets. The target antigen(s) involved in this immunopathological process has not been identified. Our strategy was to determine whether expression of a novel surface antigen by murine pancreatic beta cells would result in insulin-dependent diabetes mellitus. We have generated lines of transgenic mice (RIP-HA) that express the hemagglutinin of the A/Japan/305/57 strain of influenza virus on their insulin-producing beta cells. Hyperglycemia developed in mice derived from all three founders at a frequency varying from 13% to 27%, and was associated with lymphocytic infiltration of the islets and a humoral response against beta cell antigens, including hemagglutinin. These results suggest that the RIP-HA mice should provide a useful system in which to study the cellular interactions involved in the induction of self-tolerance and autoimmunity.
Roman
L M
LM
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas.
Simons
L F
LF
Hammer
R E
RE
Sambrook
J F
JF
Gething
M J
MJ
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010375:Pedigree; D014759:Viral Envelope Proteins / Q000235:genetics
D001323:Autoantibodies; D001786:Blood Glucose; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D014759:Viral Envelope Proteins; C024211:islet cell antibody