Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism

Westmuckett, Andrew D., Siefert, Joseph C., Tesiram, Yasvir A., Pinson, David M. and Moore, Kevin L. (2013) Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism. PLoS One, 8 8: 71822.1-71822.13. doi:10.1371/journal.pone.0071822

Author Westmuckett, Andrew D.
Siefert, Joseph C.
Tesiram, Yasvir A.
Pinson, David M.
Moore, Kevin L.
Title Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism
Formatted title
Salivary Gland Hypofunction in tyrosylprotein sulfotransferase-2 Knockout Mice Is Due to Primary Hypothyroidism
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-08
Sub-type Article (original research)
DOI 10.1371/journal.pone.0071822
Open Access Status DOI
Volume 8
Issue 8
Start page 71822.1
End page 71822.13
Total pages 13
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
Background: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice.

Methodology/Principal Findings: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were ≈ 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation.

Conclusions/Significance: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Centre for Advanced Imaging Publications
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