Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy

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Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy. / 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.

I: Proteomics - Clinical Applications, Bind 14, Nr. 6, 1900072, 11.2020.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Lukassen, MV, Poulsen, ET, Donaghy, J, Mogensen, EH, Christie, KA, Roshanravan, H, DeDioniso, L, Nesbit, MA, Moore, T & Enghild, JJ 2020, 'Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy', Proteomics - Clinical Applications, bind 14, nr. 6, 1900072. https://doi.org/10.1002/prca.201900072

APA

Lukassen, M. V., Poulsen, E. T., Donaghy, J., Mogensen, E. H., Christie, K. A., Roshanravan, H., DeDioniso, L., Nesbit, M. A., Moore, T., & Enghild, J. J. (2020). Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy. Proteomics - Clinical Applications, 14(6), [1900072]. https://doi.org/10.1002/prca.201900072

CBE

Lukassen MV, Poulsen ET, Donaghy J, Mogensen EH, Christie KA, Roshanravan H, DeDioniso L, Nesbit MA, Moore T, Enghild JJ. 2020. Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy. Proteomics - Clinical Applications. 14(6):Article 1900072. https://doi.org/10.1002/prca.201900072

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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. / Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy. I: Proteomics - Clinical Applications. 2020 ; Bind 14, Nr. 6.

Bibtex

@article{2af744cb073e44dbba5abcbe2c253f0d,
title = "Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy",
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.",
keywords = "2DE immunoblotting, cornea, granular corneal dystrophy type 2, label-free quantification, transforming growth factor β-induced protein",
author = "Lukassen, {Marie V.} and Poulsen, {Ebbe T.} and Jack Donaghy and Mogensen, {Emilie H.} and Christie, {Kathleen A.} and Hila Roshanravan and Larry DeDioniso and Nesbit, {M. Andrew} and Tara Moore and Enghild, {Jan J.}",
year = "2020",
month = nov,
doi = "10.1002/prca.201900072",
language = "English",
volume = "14",
journal = "Proteomics - Clinical Applications",
issn = "1862-8346",
publisher = "Wiley - V C H Verlag GmbH & Co. KGaA",
number = "6",

}

RIS

TY - JOUR

T1 - Protein Analysis of the TGFBIR124H Mouse Model Gives Insight into Phenotype Development of Granular Corneal Dystrophy

AU - Lukassen, Marie V.

AU - Poulsen, Ebbe T.

AU - Donaghy, Jack

AU - Mogensen, Emilie H.

AU - Christie, Kathleen A.

AU - Roshanravan, Hila

AU - DeDioniso, Larry

AU - Nesbit, M. Andrew

AU - Moore, Tara

AU - Enghild, Jan J.

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

KW - 2DE immunoblotting

KW - cornea

KW - granular corneal dystrophy type 2

KW - label-free quantification

KW - transforming growth factor β-induced protein

UR - http://www.scopus.com/inward/record.url?scp=85087651970&partnerID=8YFLogxK

U2 - 10.1002/prca.201900072

DO - 10.1002/prca.201900072

M3 - Journal article

C2 - 32558206

AN - SCOPUS:85087651970

VL - 14

JO - Proteomics - Clinical Applications

JF - Proteomics - Clinical Applications

SN - 1862-8346

IS - 6

M1 - 1900072

ER -