Impaired development of the Harderian gland in mutant protein phosphatase 2A transgenic mice

Andreas Schild, Stefan Isenmann, Naoyuki Tanimoto, Felix Tonagel, Mathias W. Seeliger, Lars M. Ittner, Alexandra Kretz, Egon Ogris, Jürgen Götz*

*Corresponding author for this work

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Although Harderian glands are especially large in rodents, many features of this retroocular gland, including its development and function, are not well established. Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes expressed in this gland. PP2A substrate specificity is determined by regulatory subunits with leucine 309 of the catalytic subunit playing a crucial role in the recruitment of regulatory subunits into the complex in vitro. Here we expressed an L309A mutant catalytic subunit in Harderian gland of transgenic mice. We found a delayed postnatal development and hypoplasia of the gland, causing enophthalmos. To determine why expression of the L309A mutant caused this phenotype, we determined the PP2A subunit composition. We found an altered subunit composition in the transgenic gland that was accompanied by pronounced changes of proteins regulating cell adhesion. Specifically, cadherin and β-catenin were dramatically reduced and shifted to the cytosol. Furthermore, we found an inactivating phosphorylation of the cadherin-directed glycogen synthase kinase-3β. In conclusion, the carboxy-terminal leucine L309 of the PP2A catalytic subunit determines PP2A heterotrimer composition in vivo. Moreover, our data demonstrate that PP2A subunit composition plays a crucial role in regulating cell adhesion and as a consequence in the development of the Harderian gland.

Original languageEnglish
Pages (from-to)362-371
Number of pages10
JournalMechanisms of Development
Volume123
Issue number5
DOIs
Publication statusPublished - 1 May 2006
Externally publishedYes

Keywords

  • Cadherin
  • Cell adhesion
  • Development
  • Enophthalmos
  • Ganzfeld electroretinography (ERG)
  • Harderian gland
  • Protein phosphatase 2A (PP2A)
  • Scanning laser ophthalmoscopy
  • Transgenic mice

Fingerprint Dive into the research topics of 'Impaired development of the Harderian gland in mutant protein phosphatase 2A transgenic mice'. Together they form a unique fingerprint.

Cite this