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.
Bibliographical noteFunding 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.
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- 2DE immunoblotting
- granular corneal dystrophy type 2
- label-free quantification
- transforming growth factor β-induced protein