Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism

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...

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Veröffentlicht in:PloS one 2013-08, Vol.8 (8), p.e71822-e71822
Hauptverfasser: Westmuckett, Andrew D, Siefert, Joseph C, Tesiram, Yasvir A, Pinson, David M, Moore, Kevin L
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Siefert, Joseph C
Tesiram, Yasvir A
Pinson, David M
Moore, Kevin L
description 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. 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. Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.
doi_str_mv 10.1371/journal.pone.0071822
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Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Meteorological &amp; Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest advanced technologies &amp; aerospace journals</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Westmuckett, Andrew D</au><au>Siefert, Joseph C</au><au>Tesiram, Yasvir A</au><au>Pinson, David M</au><au>Moore, Kevin L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-08-07</date><risdate>2013</risdate><volume>8</volume><issue>8</issue><spage>e71822</spage><epage>e71822</epage><pages>e71822-e71822</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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. 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. Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23951251</pmid><doi>10.1371/journal.pone.0071822</doi><tpages>e71822</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2013-08, Vol.8 (8), p.e71822-e71822
issn 1932-6203
1932-6203
language eng
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source MEDLINE; Public Library of Science; Full-Text Journals in Chemistry (Open access); PubMed Central; Directory of Open Access Journals; EZB Electronic Journals Library
subjects Amylases
Animals
Biology
Blotting, Western
Body weight
Body Weight - drug effects
Body Weight - genetics
Body Weight - physiology
Cloning
Dietary Supplements
Eggs
Enzymes
Exocrine glands
Female
Females
Gene Expression
Glands
Glycoproteins
Golgi apparatus
Health sciences
Hypothyroidism
Hypothyroidism - blood
Hypothyroidism - genetics
Hypothyroidism - metabolism
Infertility
Laboratory animals
Magnetic resonance
Magnetic Resonance Imaging
Male
Males
Medical research
Membrane proteins
Mice
Mice, 129 Strain
Mice, Knockout
Motility
NMR
Nuclear magnetic resonance
Pilocarpine
Post-translation
Post-translational modifications
Proteins
Reverse Transcriptase Polymerase Chain Reaction
Rodents
Saliva
Salivary alpha-Amylases - metabolism
Salivary gland
Salivary glands
Salivary Glands - metabolism
Salivary Glands - pathology
Salivary Glands - physiopathology
Secretory vesicles
Sperm
Structure-function relationships
Submandibular gland
Submandibular Gland - metabolism
Submandibular Gland - pathology
Submandibular Gland - physiopathology
Sulfation
Sulfotransferase
Sulfotransferases - genetics
Sulfotransferases - metabolism
Thyroid
Thyroid (USP) - administration & dosage
Thyroid (USP) - pharmacology
Thyroid gland
Thyroid hormones
Thyroxine
Thyroxine - blood
Tubules
Tyrosine
Western blotting
α-Amylase
title Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism
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