MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, B. S.
Right arrow Articles by Johnson, R. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, B. S.
Right arrow Articles by Johnson, R. L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2001, p. 7707-7713, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7707-7713.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function

Byong Su Kim,1 Olga V. Savinova,2 Mark V. Reedy,1 Janice Martin,2 Yi Lun,1 Lin Gan,1,3 Richard S. Smith,2,4 Stanislav I. Tomarev,5 Simon W. M. John,2,4,6 and Randy L. Johnson1,7,*

Department of Biochemistry and Molecular Biology1 and Program in Genes and Development,7 University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030; The Jackson Laboratory2 and The Howard Hughes Medical Institute,4 Bar Harbor, Maine 04609; Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 208925; Department of Ophthalmology Tufts University School of Medicine, Boston, Massachusetts 021116; and Center for Aging and Developmental Biology, University of Rochester, Rochester, New York 146423

Received 4 April 2001/Returned for modification 10 July 2001/Accepted 6 August 2001

Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been found in the trabecular meshwork inducible glucocorticoid response gene (TIGR), also known as the myocilin gene (MYOC), at the GLC1A locus on chromosome 1q21-q31. These mutations occurred in a subset of patients with juvenile- and adult-onset POAG and exhibited autosomal dominant inheritance. Ocular expression and its involvement in POAG suggest that TIGR/MYOC may have a role(s) in regulating intraocular pressure (IOP). Here, we report the generation and analysis of mice heterozygous and homozygous for a targeted null mutation in Myoc. Our study shows that Myoc mutant mice are both viable and fertile. Our in vivo findings further demonstrate that Myoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in both Myoc-heterozygous and Myoc-null mice suggests that haploinsufficiency is not a critical mechanism for POAG in individuals with mutations in MYOC. Instead, disease-causing mutations in humans likely act by gain of function.

* Corresponding author. Mailing address: Box 117, Department of Biochemistry and Molecular Biology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030. Phone: (713) 792-2551. Fax: (713) 791-9478. E-mail: rjohnson{at}odin.mdacc.tmc.edu.

Molecular and Cellular Biology, November 2001, p. 7707-7713, Vol. 21, No. 22
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.22.7707-7713.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2001 by the American Society for Microbiology. All rights reserved.