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

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Published in:	Molecular and Cellular Biology Vol. 21; no. 22; pp. 7707 - 7713
Main Authors:	Kim, Byong Su, Savinova, Olga V., Reedy, Mark V., Martin, Janice, Lun, Yi, Gan, Lin, Smith, Richard S., Tomarev, Stanislav I., John, Simon W. M., Johnson, Randy L.
Format:	Journal Article
Language:	English
Published:	United States American Society for Microbiology 01-11-2001 Taylor & Francis
Subjects:	Animals Cytoskeletal Proteins Eye - metabolism Eye - pathology Eye Proteins - genetics Eye Proteins - physiology Gene Expression Gene Targeting - methods Glaucoma, Open-Angle - pathology GLC1A gene Glycoproteins - genetics Glycoproteins - physiology Humans Intraocular Pressure Mammalian Genetic Models with Minimal or Complex Phenotypes Mice Mice, Inbred C57BL Mice, Knockout Mutagenesis Myoc gene Myocilin RNA, Messenger TIGR gene
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Abstract	Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB
AbstractList	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. 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 GLC1Alocus 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 thatMyoc is not required for normal IOP or normal ocular morphology. The lack of a discernable phenotype in bothMyoc-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. 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. Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter current issue Spotlights in the Current Issue MCB About MCB Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy MCB RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0270-7306 Online ISSN: 1098-5549 Copyright © 2014 by the American Society for Microbiology. For an alternate route to MCB .asm.org, visit: MCB
Author	Mark V. Reedy Lin Gan Yi Lun Simon W. M. John Byong Su Kim Stanislav I. Tomarev Richard S. Smith Janice Martin Randy L. Johnson Olga V. Savinova
AuthorAffiliation	Department of Biochemistry and Molecular Biology 1 and Program in Genes and Development, 7 University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030; The Jackson Laboratory 2 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 20892 5 ; Department of Ophthalmology Tufts University School of Medicine, Boston, Massachusetts 02111 6 ; and Center for Aging and Developmental Biology, University of Rochester, Rochester, New York 14642 3
AuthorAffiliation_xml	– name: Department of Biochemistry and Molecular Biology 1 and Program in Genes and Development, 7 University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030; The Jackson Laboratory 2 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 20892 5 ; Department of Ophthalmology Tufts University School of Medicine, Boston, Massachusetts 02111 6 ; and Center for Aging and Developmental Biology, University of Rochester, Rochester, New York 14642 3
Author_xml	– sequence: 1 givenname: Byong Su surname: Kim fullname: Kim, Byong Su organization: Department of Biochemistry and Molecular Biology – sequence: 2 givenname: Olga V. surname: Savinova fullname: Savinova, Olga V. organization: The Jackson Laboratory – sequence: 3 givenname: Mark V. surname: Reedy fullname: Reedy, Mark V. organization: Department of Biochemistry and Molecular Biology – sequence: 4 givenname: Janice surname: Martin fullname: Martin, Janice organization: The Jackson Laboratory – sequence: 5 givenname: Yi surname: Lun fullname: Lun, Yi organization: Department of Biochemistry and Molecular Biology – sequence: 6 givenname: Lin surname: Gan fullname: Gan, Lin organization: Center for Aging and Developmental Biology, University of Rochester – sequence: 7 givenname: Richard S. surname: Smith fullname: Smith, Richard S. organization: The Howard Hughes Medical Institute – sequence: 8 givenname: Stanislav I. surname: Tomarev fullname: Tomarev, Stanislav I. organization: Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health – sequence: 9 givenname: Simon W. M. surname: John fullname: John, Simon W. M. organization: Department of Ophthalmology Tufts University School of Medicine – sequence: 10 givenname: Randy L. surname: Johnson fullname: Johnson, Randy L. email: rjohnson@odin.mdacc.tmc.edu organization: Program in Genes and Development, University of Texas, M. D. Anderson Cancer Center
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/11604506$$D View this record in MEDLINE/PubMed
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Cites_doi	10.1093/hmg/6.12.2091 10.1038/493 10.1093/hmg/6.3.457 10.1038/1203 10.1093/hmg/10.2.117 10.1016/S1350-9462(98)00011-1 10.1006/bbrc.1998.8917 10.3109/13816819709057124 10.1006/bbrc.1998.8541 10.1093/hmg/7.7.1113 10.1093/hmg/9.7.1021 10.1038/ng0598-51 10.1093/hmg/7.7.1091 10.1073/pnas.90.10.4655 10.1006/geno.1997.4682 10.1186/1471-213X-1-3 10.1038/ng0294-168 10.1016/S0169-328X(99)00085-6 10.1074/jbc.273.11.6341 10.1136/jmg.35.12.989 10.1006/dbio.1999.9314 10.1017/S0016672300004584 10.1016/S0092-8674(00)81527-5 10.1159/000310780 10.1086/301612 10.1007/s003359900844 10.1006/dbio.1996.0330 10.1126/science.275.5300.668
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Copyright	Copyright © 2001 American Society for Microbiology 2001 Copyright © 2001, American Society for Microbiology 2001
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Notes	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 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@odin.mdacc.tmc.edu.
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References	9618168 - Hum Mol Genet. 1998 Jul;7(7):1113-7 10571183 - Cell. 1999 Nov 12;99(4):409-19 9618165 - Hum Mol Genet. 1998 Jul;7(7):1091-8 9620769 - Nat Genet. 1998 Jun;19(2):140-7 10711688 - Invest Ophthalmol Vis Sci. 2000 Mar;41(3):729-40 11152659 - Hum Mol Genet. 2001 Jan 15;10(2):117-25 11228591 - BMC Dev Biol. 2001;1:3 10320784 - Brain Res Mol Brain Res. 1999 May 7;68(1-2):64-72 9328473 - Hum Mol Genet. 1997 Nov;6(12):2091-7 9680392 - Mamm Genome. 1998 Aug;9(8):673-5 9920500 - Prog Retin Eye Res. 1999 Jan;18(1):91-119 10395790 - Dev Biol. 1999 Jul 15;211(2):306-22 9588210 - Biochem Biophys Res Commun. 1998 Apr 28;245(3):887-93 11006633 - Genet Res. 2000 Aug;76(1):41-50 9361308 - Ophthalmic Genet. 1997 Sep;18(3):109-18 10798654 - Invest Ophthalmol Vis Sci. 2000 May;41(6):1386-91 8162071 - Nat Genet. 1994 Feb;6(2):168-73 10767326 - Hum Mol Genet. 2000 Apr 12;9(7):1021-32 9590288 - Nat Genet. 1998 May;19(1):51-5 9863594 - J Med Genet. 1998 Dec;35(12):989-92 9169133 - Genomics. 1997 May 1;41(3):360-9 9176893 - Ophthalmologica. 1997;211(3):126-39 9147650 - Hum Mol Genet. 1997 Mar;6(3):457-64 9345106 - Am J Hum Genet. 1997 Nov;61(5):1202-4 9675094 - Biochem Biophys Res Commun. 1998 Jul 9;248(1):104-9 8506313 - Proc Natl Acad Sci U S A. 1993 May 15;90(10):4655-9 9005853 - Science. 1997 Jan 31;275(5300):668-70 10493779 - Mol Vis. 1999 Sep 15;5:22 9008633 - Invest Ophthalmol Vis Sci. 1997 Jan;38(1):83-91 8954729 - Dev Biol. 1996 Dec 15;180(2):579-93 9697688 - Nat Genet. 1998 Aug;19(4):319-21 9579474 - Invest Ophthalmol Vis Sci. 1998 May;39(6):951-62 9497363 - J Biol Chem. 1998 Mar 13;273(11):6341-50 9008647 - Invest Ophthalmol Vis Sci. 1997 Jan;38(1):249-53 B20 B21 Karali A. (B13) 2000; 41 B22 B23 B26 B27 B28 B29 Hawes N. L. (B9) 1999; 5 Choplin N. T. (B6) 1998 B30 B31 B10 B32 John S. W. (B11) 1997; 38 Quigley H. A. (B24) 1997; 38 B33 B34 B35 B14 B36 B15 B17 B19 Kulak S. C. (B16) 1998; 7 Albrecht U. (B3) 1996; 180 B2 B4 B5 Shields M. B. (B25) 1997 B7 B8 John S. W. (B12) 1998; 39 Lam D. S. (B18) 2000; 41 Abderrahim H. (B1) 1998; 9
References_xml	– ident: B2 doi: 10.1093/hmg/6.12.2091 – volume: 5 start-page: 22 year: 1999 ident: B9 publication-title: Mol. Vis. contributor: fullname: Hawes N. L. – ident: B22 doi: 10.1038/493 – volume: 41 start-page: 729 year: 2000 ident: B13 publication-title: Investig. Ophthalmol. Vis. Sci. contributor: fullname: Karali A. – volume-title: Textbook of glaucoma year: 1997 ident: B25 contributor: fullname: Shields M. B. – ident: B7 doi: 10.1093/hmg/6.3.457 – ident: B20 doi: 10.1038/1203 – ident: B10 doi: 10.1093/hmg/10.2.117 – ident: B19 doi: 10.1016/S1350-9462(98)00011-1 – ident: B33 doi: 10.1006/bbrc.1998.8917 – ident: B28 doi: 10.3109/13816819709057124 – ident: B34 doi: 10.1006/bbrc.1998.8541 – volume: 7 start-page: 1113 year: 1998 ident: B16 publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/7.7.1113 contributor: fullname: Kulak S. C. – ident: B26 doi: 10.1093/hmg/9.7.1021 – ident: B5 doi: 10.1038/ng0598-51 – ident: B35 doi: 10.1093/hmg/7.7.1091 – volume-title: Atlas of glaucoma. year: 1998 ident: B6 contributor: fullname: Choplin N. T. – ident: B36 doi: 10.1073/pnas.90.10.4655 – ident: B15 doi: 10.1006/geno.1997.4682 – ident: B27 doi: 10.1186/1471-213X-1-3 – volume: 38 start-page: 249 year: 1997 ident: B11 publication-title: Investig. Ophthalmol. Vis. Sci. contributor: fullname: John S. W. – ident: B8 doi: 10.1038/ng0294-168 – ident: B32 doi: 10.1016/S0169-328X(99)00085-6 – volume: 38 start-page: 83 year: 1997 ident: B24 publication-title: Investig. Ophthalmol. Vis. Sci. contributor: fullname: Quigley H. A. – ident: B21 doi: 10.1074/jbc.273.11.6341 – ident: B29 doi: 10.1136/jmg.35.12.989 – ident: B14 doi: 10.1006/dbio.1999.9314 – ident: B17 doi: 10.1017/S0016672300004584 – ident: B4 doi: 10.1016/S0092-8674(00)81527-5 – volume: 41 start-page: 1386 year: 2000 ident: B18 publication-title: Investig. Ophthalmol. Vis. Sci. contributor: fullname: Lam D. S. – volume: 39 start-page: 951 year: 1998 ident: B12 publication-title: Investig. Ophthalmol. Vis. Sci. contributor: fullname: John S. W. – ident: B23 doi: 10.1159/000310780 – ident: B31 doi: 10.1086/301612 – volume: 9 start-page: 673 year: 1998 ident: B1 publication-title: Mamm. Genome doi: 10.1007/s003359900844 contributor: fullname: Abderrahim H. – volume: 180 start-page: 579 year: 1996 ident: B3 publication-title: Dev. Biol. doi: 10.1006/dbio.1996.0330 contributor: fullname: Albrecht U. – ident: B30 doi: 10.1126/science.275.5300.668
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Snippet	Article Usage Stats Services MCB Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley... Glaucoma is a heterogeneous eye disease and a major cause of blindness worldwide. Recently, primary open angle glaucoma (POAG)-associated mutations have been...
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StartPage	7707
SubjectTerms	Animals Cytoskeletal Proteins Eye - metabolism Eye - pathology Eye Proteins - genetics Eye Proteins - physiology Gene Expression Gene Targeting - methods Glaucoma, Open-Angle - pathology GLC1A gene Glycoproteins - genetics Glycoproteins - physiology Humans Intraocular Pressure Mammalian Genetic Models with Minimal or Complex Phenotypes Mice Mice, Inbred C57BL Mice, Knockout Mutagenesis Myoc gene Myocilin RNA, Messenger TIGR gene
Title	Targeted Disruption of the Myocilin Gene (Myoc) Suggests that Human Glaucoma-Causing Mutations Are Gain of Function
URI	http://mcb.asm.org/content/21/22/7707.abstract https://www.tandfonline.com/doi/abs/10.1128/MCB.21.22.7707-7713.2001 https://www.ncbi.nlm.nih.gov/pubmed/11604506 https://search.proquest.com/docview/18208018 https://pubmed.ncbi.nlm.nih.gov/PMC99941
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