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

Schild, Andreas, Isenmann, Stefan, Tanimoto, Naoyuki, Tonagel, Felix, Seeliger, Mathias W., Ittner, Lars M., Kretz, Alexandra, Ogris, Egon and Gotz, Juergen (2006) Impaired development of the Harderian gland in mutant protein phosphatase 2A transgenic mice. Mechanisms of Development, 123 5: 362-371. doi:10.1016/j.mod.2006.03.003


Author Schild, Andreas
Isenmann, Stefan
Tanimoto, Naoyuki
Tonagel, Felix
Seeliger, Mathias W.
Ittner, Lars M.
Kretz, Alexandra
Ogris, Egon
Gotz, Juergen
Title Impaired development of the Harderian gland in mutant protein phosphatase 2A transgenic mice
Journal name Mechanisms of Development   Check publisher's open access policy
ISSN 0925-4773
1872-6356
Publication date 2006-05
Sub-type Article (original research)
DOI 10.1016/j.mod.2006.03.003
Open Access Status Not yet assessed
Volume 123
Issue 5
Start page 362
End page 371
Total pages 10
Place of publication E Park, Shannon, Clare Ireland
Publisher Elsevier Ireland
Language eng
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.
Keyword Cadherin
Cell adhesion
Development
Enophthalmos
Ganzfeld electroretinography (ERG)
Harderian gland
Protein phosphatase 2A (PP2A)
Scanning laser ophthalmoscopy
Transgenic mice
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Centre for Ageing Dementia Research Publications
 
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