@article{f1e60a85f01548f194d38f17c7ac8fe7,
title = "Targeted TNF-α Overexpression Drives Salivary Gland Inflammation",
abstract = "Chronic inflammation of the salivary glands from pathologic conditions such as Sj{\"o}gren{\textquoteright}s syndrome can result in glandular destruction and hyposalivation. To understand which molecular factors may play a role in clinical cases of salivary gland hypofunction, we developed an aquaporin 5 (AQP5) Cre mouse line to produce genetic recombination predominantly within the acinar cells of the glands. We then bred these mice with the TNF-αglo transgenic line to develop a mouse model with salivary gland–specific overexpression of TNF-α; which replicates conditions seen in sialadenitis, an inflammation of the salivary glands resulting from infection or autoimmune disorders such as Sj{\"o}gren{\textquoteright}s syndrome. The resulting AQP5-Cre/TNF-αglo mice display severe inflammation in the salivary glands with acinar cell atrophy, fibrosis, and dilation of the ducts. AQP5 expression was reduced in the salivary glands, while tight junction integrity appeared to be disrupted. The immune dysregulation in the salivary gland of these mice led to hyposalivation and masticatory dysfunction.",
keywords = "acinar cells, aquaporin 5, sialadenitis, tight junctions, transgenic mouse, xerostomia",
author = "A. Limaye and Hall, {B. E.} and L. Zhang and A. Cho and M. Prochazkova and C. Zheng and M. Walker and F. Adewusi and Burbelo, {P. D.} and Sun, {Z. J.} and Ambudkar, {I. S.} and Dolan, {J. C.} and Schmidt, {B. L.} and Kulkarni, {A. B.}",
note = "Funding Information: This work was supported by the Division of Intramural Research of the National Institute of Dental and Craniofacial Research, National Institutes of Health. We thank Dr. Kenneth Yamada for critical reading of the manuscript, Niklas Malmstrom for technical assistance, and the Veterinary Resource Core, the Gene Transfer Core, and the Combined Technical Research Core of the Division of Intramural Research for providing expert support. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. Funding Information: We thank Dr. Kenneth Yamada for critical reading of the manuscript, Niklas Malmstrom for technical assistance, and the Veterinary Resource Core, the Gene Transfer Core, and the Combined Technical Research Core of the Division of Intramural Research for providing expert support. Publisher Copyright: {\textcopyright} International & American Associations for Dental Research 2019.",
year = "2019",
month = jun,
day = "1",
doi = "10.1177/0022034519837240",
language = "English (US)",
volume = "98",
pages = "713--719",
journal = "Journal of Dental Research",
issn = "0022-0345",
publisher = "SAGE Publications Inc.",
number = "6",
}