Hypothyroidism in transgenic mice expressing IFN-gamma in the thyroid.
IFN-gamma has been implicated with contradictory results in the pathogenetic process of autoimmune (Hashimoto's) thyroiditis, the most common cause of hypothyroidism in adults. To test whether the local production of IFN-gamma can lead to thyroid dysfunction, we have generated transgenic mice that express constitutively IFN-gamma in the thyroid follicular cells. This expression resulted in severe hypothyroidism, with growth retardation and disruption of the thyroid architecture. The hypothyroidism derived from a profound inhibition of the expression of the sodium iodide symporter gene. Taken together, these results indicate a direct role of IFN-gamma in the thyroid dysfunction that occurs in autoimmune thyroiditis.
Caturegli
P
P
Department of Pathology, School of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA. pcat@jhmi.edu
Hejazi
M
M
Suzuki
K
K
Dohan
O
O
Carrasco
N
N
Kohn
L D
LD
Rose
N R
NR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006651:Histocytochemistry; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics* / Q000276:immunology; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D012974:Sodium Iodide / Q000378:metabolism; D013961:Thyroid Gland / Q000276:immunology / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000235:genetics* / Q000276:immunology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood
D002352:Carrier Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D007371:Interferon-gamma; D013972:Thyrotropin; D012974:Sodium Iodide; D013974:Thyroxine