HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Malyukova, I. Articles by Tomarev, S. I. Search for Related Content PubMed PubMed Citation Articles by Malyukova, I. Articles by Tomarev, S. I.

Mutated Mouse and Human Myocilins Have Similar Properties and Do Not Block General Secretory Pathway

¹From the Section of Molecular Mechanisms of Glaucoma, Laboratory of Molecular and Developmental Biology, and the ²Biological Imaging Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland.

PURPOSE. The present study compared properties of wild-type and mutated mouse and human myocilin (Myoc) proteins as a prerequisite for development of a mouse model of glaucoma.

METHODS. cDNA encoding full-length mouse Myoc was cloned into the p3XFLAG-CMV-14 vector. Tyr423His and Ile463Ser mutations were introduced into the mouse Myoc protein by in vitro mutagenesis. Intracellular localization and secretion of wild-type and mutated mouse Myoc proteins were studied in immunostaining and Western blotting experiments, respectively, after transfection into COS-7 cells.

RESULTS. Similar to human MYOC, wild-type and mutated mouse Myoc demonstrated vesicular staining in transfected cells. However, while wild-type human and mouse Myoc were preferentially located in both the endoplasmic reticulum and Golgi, mutated human and mouse Myoc were located mainly in the endoplasmic reticulum and were excluded from Golgi. Similar to mutations in human MYOC, mutations in mouse Myoc dramatically reduced its secretion from transfected cells. Secretion of mutated Myoc was partially restored by culturing cells at 30°C instead of 37°C. The presence of mutated human MYOC prevented secretion of wild-type mouse Myoc but did not dramatically affect secretion of alkaline phosphatase, thrombospondin, Timp3 or olfactomedin-1.

CONCLUSIONS. Properties of the mouse Myoc protein are similar to those of the human MYOC. The presence of mutated mouse or human Myoc does not block a general secretory pathway. Expression of mutated Myoc in the eye in mice may mimic human glaucoma and lead to development of a genetic mouse model of glaucoma.

This article has been cited by other articles:

				Y. Zhou, O. Grinchuk, and S. I. Tomarev Transgenic Mice Expressing the Tyr437His Mutant of Human Myocilin Protein Develop Glaucoma Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 1932 - 1939. [Abstract] [Full Text] [PDF]

				D. B. Gould, M. Reedy, L. A. Wilson, R. S. Smith, R. L. Johnson, and S. W. M. John Mutant Myocilin Nonsecretion In Vivo Is Not Sufficient To Cause Glaucoma Mol. Cell. Biol., November 15, 2006; 26(22): 8427 - 8436. [Abstract] [Full Text] [PDF]

				V. Senatorov, I. Malyukova, R. Fariss, E. F. Wawrousek, S. Swaminathan, S. K. Sharan, and S. Tomarev Expression of Mutated Mouse Myocilin Induces Open-Angle Glaucoma in Transgenic Mice. J. Neurosci., November 15, 2006; 26(46): 11903 - 11914. [Abstract] [Full Text] [PDF]