Protein Analysis of the TGFBI R124H Mouse Model Gives Insight Into Phenotype Development of Granular Corneal Dystrophy

Marie V. Lukassen, Ebbe Toftgaard Poulsen, Jack Donaghy, Emilie Hage Mogensen, Kathleen A. Christie, Hila Roshanravan, Larry DeDionisio, M. Andrew Nesbit, Tara C. B. Moore, Jan J Enghild

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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.
Original languageEnglish
Article number1900072
JournalPROTEOMICS - Clinical Applications
Issue number6
Early online date18 Jun 2020
Publication statusPublished online - 18 Jun 2020

Bibliographical note

Funding Information:
The authors thank Dr. Shigeto Shimmura (Keio University School of Medicine) and Dr. Eung Kweon Kim (Yonsei University College of Medicine) for sharing of the TGFBI R124H mouse model. The project was supported by the VELUX Foundation (00014557), Danish Council for Independent Research—Medical Sciences (DFF‐4004‐00471), the Novo Nordisk Foundation (Bio‐MS), and Dagmar Marshalls Fond.

Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Copyright 2021 Elsevier B.V., All rights reserved.


  • 2DE immunoblotting
  • cornea
  • granular corneal dystrophy type 2
  • label-free quantification
  • transforming growth factor β-induced protein


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