No apparent damage in the thyroid of transgenic mice expressing antiapoptotic FLIP.
FLIP is an antiapoptotic protein that has been demonstrated to play an important role in inflammation, cancer, and autoimmune diseases. However, it is not known whether increased expression of FLIP (FLICE inhibitory protein) in thyrocytes would alter the development of the thyroid and/or pathogenesis of thyroiditis. To examine the effects of overexpression of this antiapoptotic molecule on the thyroid, we have developed transgenic mouse lines that specifically express FLIP in thyrocytes. A DNA construct designed with an in-frame coding sequence for the E8 protein, a viral FLIP, was put under the control of the thyroglobulin (Tg) promoter (the Tg-FLIP transgene). In 8 of 12 resultant transgenic mouse lines, FLIP expression in thyrocytes driven by the Tg promoter was documented, and confirmed at RNA and protein levels. These Tg-FLIP transgenic mice were monitored for 1 year. Throughout the entire observation period, the transgenic mice remained alive and healthy without evidence of thyroid dysfunction. Adult mice were able to breed. Histologic examination of thyroids obtained at various time points did not reveal significant differences between transgenic mice and their control littermates. Therefore, transgenic mice with thyrocyte-specific expression of FLIP have normal thyroid development with no significant changes in thyroid cell death or proliferation.
Wang
Su He
SH
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0648, USA.
Arscott
Patricia
P
Wu
Peiqing
P
Baker
James R
JR
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015139:Blotting, Southern; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000254:growth & development / Q000473:pathology / Q000502:physiology*; D019076:Transgenes / Q000235:genetics
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506387:Cflar protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D012313:RNA