IADR Abstract Archives

Targeted Overexpression of TGF-β1 Disrupts Function of Mouse Salivary Glands

Objective: Salivary gland development and physiology can be affected by perturbations in the transforming growth factor-β (TGF-β) signaling pathway. TGF-β signaling can influence branching morphogenesis, ECM deposition, and immune homeostasis. Using Cre/loxP technology, we have created mouse models to determine the precise role of TGF-β signaling in the salivary gland. Methods: We have generated a mouse that allows for conditional overexpression of TGF-β1 (β1glo) in order to study its role in salivary gland homeostasis. Transgenic TGF-β1 expression occurs through breeding the β1glo mice to a mouse mammary tumor virus (MMTV)-Cre (MC) transgenic line, since these mice show strong, but not exclusive, recombination in the salivary gland. Results: The resulting β1glo/MC mice that were born show dysplastic growth in the salivary gland, with the appearance of reduced branching and increased mesenchyme. Over time, the increased TGF-β signaling resulted in atrophy of both the granular convoluted ducts (GCDs) and the acini. Fibrosis of the salivary gland was also distinctly present, with excess deposition of collagens and other extracellular matrix proteins. The β1glo/MC mice also had observable hyposalivation resulting from the fibrosis and atrophy within the salivary gland. Conclusions: These results further implicate TGF-β in pathological cases of salivary gland inflammation and fibrosis that occur with chronic infections in the glands, with autoimmune diseases such as Sjögren's syndrome, or with the radiation therapy given to head-and-neck cancer patients. Support Information: Supported by the Division of Intramural Research, NIDCR, NIH Z01DE000698-10.
AADR/CADR Annual Meeting
2010 AADR/CADR Annual Meeting (Washington, D.C.)
Washington, D.C.
2010
63
Salivary Research
  • Hall, Bradford  ( National Institute of Health, Bethesda, MD, USA )
  • Kulkarni, Ashok B.  ( National Institute of Health, Bethesda, MD, USA )
  • Zheng, Changyu  ( National Institute of Health, Bethesda, MD, USA )
  • Swaim, William D.  ( National Institute of Health, Bethesda, MD, USA )
  • Cho, Andrew  ( National Institute of Health, Bethesda, MD, USA )
  • Nagineni, Chandrasekharam N.  ( National Institute of Health, Bethesda, MD, USA )
  • Eckhaus, Michael A.  ( National Institute of Health, Bethesda, MD, USA )
  • Flanders, Kathleen C.  ( National Institute of Health, Bethesda, MD, USA )
  • Ambudkar, Indu S.  ( National Institute of Health, Bethesda, MD, USA )
  • Baum, Bruce J.  ( National Institute of Health, Bethesda, MD, USA )
    • Oral Session
    Salivary Gland Development I
    03/03/2010