Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy
Purpose Mutations in the transforming growth factor β‐induced protein (TGFBIp) are associated with TGFBI‐linked corneal dystrophies, which manifests as protein deposits in the cornea. A total of 70 different disease‐causing mutations have been reported so far including the common R124H substitution,...
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| Veröffentlicht in: | Proteomics. Clinical applications 2020-11, Vol.14 (6), p.e1900072-n/a |
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| creator | Lukassen, Marie V. Poulsen, Ebbe T. Donaghy, Jack Mogensen, Emilie H. Christie, Kathleen A. Roshanravan, Hila DeDioniso, Larry Nesbit, M. Andrew Moore, Tara Enghild, Jan J. |
| description | Purpose
Mutations in the transforming growth factor β‐induced protein (TGFBIp) are associated with TGFBI‐linked corneal dystrophies, which manifests as protein deposits in the cornea. A total of 70 different disease‐causing mutations have been reported so far including the common R124H substitution, which is associated with granular corneal dystrophy type 2 (GCD2). The disease mechanism of GCD2 is not known and the current treatments only offer temporary relief due to the reoccurrence of deposits.
Experimental Design
The corneal protein profiles of the three genotypes (wild‐type (WT), heterozygotes, and homozygotes) of a GCD2 mouse model are compared using label‐free quantitative LC‐MS/MS.
Results
The mice do not display corneal protein deposits and the global protein expression between the three genotypes is highly similar. However, the expression of mutated TGFBIp is 41% of that of the WT protein.
Conclusions and Clinical Relevance
It is proposed that the lowered expression level of mutant TGFBIp protein relative to WT protein is the direct cause of the missing development of corneal deposits in the mouse. The overall protein profiles of the corneas are not impacted by the reduced amount of TGFBIp. Altogether, this supports a partial reduction in mutated TGFBIp as a potential treatment strategy for GCD2. |
| doi_str_mv | 10.1002/prca.201900072 |
| format | Article |
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Mutations in the transforming growth factor β‐induced protein (TGFBIp) are associated with TGFBI‐linked corneal dystrophies, which manifests as protein deposits in the cornea. A total of 70 different disease‐causing mutations have been reported so far including the common R124H substitution, which is associated with granular corneal dystrophy type 2 (GCD2). The disease mechanism of GCD2 is not known and the current treatments only offer temporary relief due to the reoccurrence of deposits.
Experimental Design
The corneal protein profiles of the three genotypes (wild‐type (WT), heterozygotes, and homozygotes) of a GCD2 mouse model are compared using label‐free quantitative LC‐MS/MS.
Results
The mice do not display corneal protein deposits and the global protein expression between the three genotypes is highly similar. However, the expression of mutated TGFBIp is 41% of that of the WT protein.
Conclusions and Clinical Relevance
It is proposed that the lowered expression level of mutant TGFBIp protein relative to WT protein is the direct cause of the missing development of corneal deposits in the mouse. The overall protein profiles of the corneas are not impacted by the reduced amount of TGFBIp. Altogether, this supports a partial reduction in mutated TGFBIp as a potential treatment strategy for GCD2.</description><identifier>ISSN: 1862-8346</identifier><identifier>EISSN: 1862-8354</identifier><identifier>DOI: 10.1002/prca.201900072</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>2DE immunoblotting ; Cornea ; Corneal dystrophy ; Deposits ; Design of experiments ; Genotypes ; granular corneal dystrophy type 2 ; Growth factors ; Heterozygotes ; Homozygotes ; label‐free quantification ; Mutation ; Phenotypes ; Proteins ; transforming growth factor β‐induced protein ; Transforming growth factor-b</subject><ispartof>Proteomics. Clinical applications, 2020-11, Vol.14 (6), p.e1900072-n/a</ispartof><rights>2020 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2020 Wiley‐VCH GmbH</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-9292-9172</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fprca.201900072$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fprca.201900072$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Lukassen, Marie V.</creatorcontrib><creatorcontrib>Poulsen, Ebbe T.</creatorcontrib><creatorcontrib>Donaghy, Jack</creatorcontrib><creatorcontrib>Mogensen, Emilie H.</creatorcontrib><creatorcontrib>Christie, Kathleen A.</creatorcontrib><creatorcontrib>Roshanravan, Hila</creatorcontrib><creatorcontrib>DeDioniso, Larry</creatorcontrib><creatorcontrib>Nesbit, M. Andrew</creatorcontrib><creatorcontrib>Moore, Tara</creatorcontrib><creatorcontrib>Enghild, Jan J.</creatorcontrib><title>Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy</title><title>Proteomics. Clinical applications</title><description>Purpose
Mutations in the transforming growth factor β‐induced protein (TGFBIp) are associated with TGFBI‐linked corneal dystrophies, which manifests as protein deposits in the cornea. A total of 70 different disease‐causing mutations have been reported so far including the common R124H substitution, which is associated with granular corneal dystrophy type 2 (GCD2). The disease mechanism of GCD2 is not known and the current treatments only offer temporary relief due to the reoccurrence of deposits.
Experimental Design
The corneal protein profiles of the three genotypes (wild‐type (WT), heterozygotes, and homozygotes) of a GCD2 mouse model are compared using label‐free quantitative LC‐MS/MS.
Results
The mice do not display corneal protein deposits and the global protein expression between the three genotypes is highly similar. However, the expression of mutated TGFBIp is 41% of that of the WT protein.
Conclusions and Clinical Relevance
It is proposed that the lowered expression level of mutant TGFBIp protein relative to WT protein is the direct cause of the missing development of corneal deposits in the mouse. The overall protein profiles of the corneas are not impacted by the reduced amount of TGFBIp. Altogether, this supports a partial reduction in mutated TGFBIp as a potential treatment strategy for GCD2.</description><subject>2DE immunoblotting</subject><subject>Cornea</subject><subject>Corneal dystrophy</subject><subject>Deposits</subject><subject>Design of experiments</subject><subject>Genotypes</subject><subject>granular corneal dystrophy type 2</subject><subject>Growth factors</subject><subject>Heterozygotes</subject><subject>Homozygotes</subject><subject>label‐free quantification</subject><subject>Mutation</subject><subject>Phenotypes</subject><subject>Proteins</subject><subject>transforming growth factor β‐induced protein</subject><subject>Transforming growth factor-b</subject><issn>1862-8346</issn><issn>1862-8354</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpdkT1PwzAQhiMEEuVjZbbEwlI4O7YTj6WlpRKICsEcOc2ZpnLtYCeg_HtSgTqw3N3w6JXufZLkisItBWB3TVjrWwZUAUDGjpIRzSUb56ngx4eby9PkLMYtgOAsg1HSrYJvsXZk4rTtYx2JN6TdIHlbzO-Xr5TxR_Lsu4jDrNCSRf2FkSxdrD82Lald68lqg863fYNkhl9ofbND1-5jFkG7zupApj441JbM-tgG32z6i-TEaBvx8m-fJ-_zh7fp4_jpZbGcTp7GDeVSjbXJVSVApVBVsgTQoqQqF2vBwVSZwVJJlqfIqcyMNFQYRImM8bw0aVmiSc-Tm9_cJvjPDmNb7Oq4Rmu1w-GpgnEqWK4yIQb0-h-69V0YStlTErJs6FgNFP-lvmuLfdGEeqdDX1Ao9gqKvYLioKBYvU4njKYq_QF4tHve</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Lukassen, Marie V.</creator><creator>Poulsen, Ebbe T.</creator><creator>Donaghy, Jack</creator><creator>Mogensen, Emilie H.</creator><creator>Christie, Kathleen A.</creator><creator>Roshanravan, Hila</creator><creator>DeDioniso, Larry</creator><creator>Nesbit, M. Andrew</creator><creator>Moore, Tara</creator><creator>Enghild, Jan J.</creator><general>Wiley Subscription Services, Inc</general><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9292-9172</orcidid></search><sort><creationdate>202011</creationdate><title>Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy</title><author>Lukassen, Marie V. ; Poulsen, Ebbe T. ; Donaghy, Jack ; Mogensen, Emilie H. ; Christie, Kathleen A. ; Roshanravan, Hila ; DeDioniso, Larry ; Nesbit, M. Andrew ; Moore, Tara ; Enghild, Jan J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p1469-af89d50930dd6b00a5b1985c540fd7feb96283e4167f6f15fee6e2248bf3bbef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>2DE immunoblotting</topic><topic>Cornea</topic><topic>Corneal dystrophy</topic><topic>Deposits</topic><topic>Design of experiments</topic><topic>Genotypes</topic><topic>granular corneal dystrophy type 2</topic><topic>Growth factors</topic><topic>Heterozygotes</topic><topic>Homozygotes</topic><topic>label‐free quantification</topic><topic>Mutation</topic><topic>Phenotypes</topic><topic>Proteins</topic><topic>transforming growth factor β‐induced protein</topic><topic>Transforming growth factor-b</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lukassen, Marie V.</creatorcontrib><creatorcontrib>Poulsen, Ebbe T.</creatorcontrib><creatorcontrib>Donaghy, Jack</creatorcontrib><creatorcontrib>Mogensen, Emilie H.</creatorcontrib><creatorcontrib>Christie, Kathleen A.</creatorcontrib><creatorcontrib>Roshanravan, Hila</creatorcontrib><creatorcontrib>DeDioniso, Larry</creatorcontrib><creatorcontrib>Nesbit, M. Andrew</creatorcontrib><creatorcontrib>Moore, Tara</creatorcontrib><creatorcontrib>Enghild, Jan J.</creatorcontrib><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Proteomics. Clinical applications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lukassen, Marie V.</au><au>Poulsen, Ebbe T.</au><au>Donaghy, Jack</au><au>Mogensen, Emilie H.</au><au>Christie, Kathleen A.</au><au>Roshanravan, Hila</au><au>DeDioniso, Larry</au><au>Nesbit, M. Andrew</au><au>Moore, Tara</au><au>Enghild, Jan J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy</atitle><jtitle>Proteomics. Clinical applications</jtitle><date>2020-11</date><risdate>2020</risdate><volume>14</volume><issue>6</issue><spage>e1900072</spage><epage>n/a</epage><pages>e1900072-n/a</pages><issn>1862-8346</issn><eissn>1862-8354</eissn><abstract>Purpose
Mutations in the transforming growth factor β‐induced protein (TGFBIp) are associated with TGFBI‐linked corneal dystrophies, which manifests as protein deposits in the cornea. A total of 70 different disease‐causing mutations have been reported so far including the common R124H substitution, which is associated with granular corneal dystrophy type 2 (GCD2). The disease mechanism of GCD2 is not known and the current treatments only offer temporary relief due to the reoccurrence of deposits.
Experimental Design
The corneal protein profiles of the three genotypes (wild‐type (WT), heterozygotes, and homozygotes) of a GCD2 mouse model are compared using label‐free quantitative LC‐MS/MS.
Results
The mice do not display corneal protein deposits and the global protein expression between the three genotypes is highly similar. However, the expression of mutated TGFBIp is 41% of that of the WT protein.
Conclusions and Clinical Relevance
It is proposed that the lowered expression level of mutant TGFBIp protein relative to WT protein is the direct cause of the missing development of corneal deposits in the mouse. The overall protein profiles of the corneas are not impacted by the reduced amount of TGFBIp. Altogether, this supports a partial reduction in mutated TGFBIp as a potential treatment strategy for GCD2.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/prca.201900072</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0001-9292-9172</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | 2DE immunoblotting Cornea Corneal dystrophy Deposits Design of experiments Genotypes granular corneal dystrophy type 2 Growth factors Heterozygotes Homozygotes label‐free quantification Mutation Phenotypes Proteins transforming growth factor β‐induced protein Transforming growth factor-b |
| title | Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy |
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