TGF-beta 1 overexpression in murine pancreas induces chronic pancreatitis and, together with TNF-alpha, triggers insulin-dependent diabetes.
We have generated transgenic mice overexpressing TGF-beta 1 in pancreatic beta cells. This resulted in massive fibrosis of the pancreas; in adult mice, most of the acini were replaced by fibrotic and adipose tissues. A conspicuous disorganization of the islets of Langerhans was also observed; however, the number of beta cells was not decreased and the mice were normoglycemic. Backcrossing to transgenic mice overexpressing TNF-alpha in their islet beta cells (which also remain normoglycemic, (1)) yielded double transgenics, most of which became diabetic by the age of 4 months; histological analysis revealed a dramatic decrease in insulin-containing beta cells.
Sanvito
F
F
Département de Morphologie, Centre Médical Universitaire, Genève 4, Switzerland.
Nichols
A
A
Herrera
P L
PL
Huarte
J
J
Wohlwend
A
A
Vassalli
J D
JD
Orci
L
L
D000681:Amylases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002908:Chronic Disease; D017931:DNA Primers / Q000737:chemistry; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010179:Pancreas / Q000378:metabolism; D010195:Pancreatitis / Q000209:etiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017931:DNA Primers; D007328:Insulin; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D000681:Amylases