sirt1-null mice develop an autoimmune-like condition.
The sirt1 gene encodes a protein deacetylase with a broad spectrum of reported substrates. Mice carrying null alleles for sirt1 are viable on outbred genetic backgrounds so we have examined them in detail to identify the biological processes that are dependent on SIRT1. Sera from adult sirt1-null mice contain antibodies that react with nuclear antigens and immune complexes become deposited in the livers and kidneys of these animals. Some of the sirt1-null animals develop a disease resembling diabetes insipidus when they approach 2 years of age although the relationship to the autoimmunity remains unclear. We interpret these observations as consistent with a role for SIRT1 in sustaining normal immune function and in this way delaying the onset of autoimmune disease.
Sequeira
Jedon
J
Center for Cancer Therapeutics, Ottawa Health Research Institute, Box 926, 3rd Floor, 501 Smyth Road, Ottawa, Ontario, Canada K1H 8L6.
Boily
Gino
G
Bazinet
Stephanie
S
Saliba
Sarah
S
He
Xiaohong
X
Jardine
Karen
K
Kennedy
Christopher
C
Staines
William
W
Rousseaux
Colin
C
Mueller
Rudi
R
McBurney
Michael W
MW
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D003919:Diabetes Insipidus / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004731:Endotoxins / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007136:Immunoglobulins / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D014556:Urine
D004731:Endotoxins; D007136:Immunoglobulins; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins