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Mutation in the βB2‐crystallin gene leads to cataracts, epithelial mesenchymal transition, and upregulation of integrins
Author(s) -
Roop Victoria H.,
Mamuya Fahmy,
Duncan Melinda K.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.909.10
Subject(s) - downregulation and upregulation , biology , crystallin , integrin , mutant , microbiology and biotechnology , genetics , gene , cell
The most abundant protein in the lens fiber cells is βB2‐crystallin (Crybb2). Mutations in the Crybb2 gene have been shown to cause cataracts in both mice and humans. A twelve nucleotide deletion in the lens epithelial cells, known as the Crybb2 Phil mutation, leads to epithelial mesenchymal transition (EMT) during development. However, the mechanism behind this phenotype is poorly understood. The aim of this project is to understand the causes and effects of mutations in βB2‐crystallin. Tissues obtained from Crybb2 Phil mutant adult mice were immunostained with αV, α2, α3, α5, α6, β1 integrin subunits, and phospo‐SMAD3. Compared to the wild type lens, β1, αV, and α5 were upregulated in the Crybb2 Phil mutant. However, no changes were seen in α2, α3, and α6 integrin subunits. Phospho‐SMAD3 and smooth muscle actin (SMA) levels were also upregulated in Crybb2 Phil mice. Upregulation of SMA signifies that the Crybb2 phil mice undergo EMT during development. Furthermore, over expression of β1 and αV integrin along with SMAD3 in these mutants suggest that the TGFβ‐SMAD interacting pathway may be involved. This project is funded by National Eye Institute grant EY015279. VR is a Charles Peter White Scholar.