HSF4 Is Required for B Crystalline Expression and Normal Lens Development

Abstract

Purpose: : Lens transparency depends on the appropriate arrangement and distribution of lens proteins. Recently, more and more mutations in HSF4 have been identified in human families with cataracts. The present study is to explore the mechanisms of HSF4 in lens development and cataract formation.

Methods: : Hsf4-null mice were used as a model. Paraffin section, semithin section and TEM (transmission electron microscope) were used to analyze the lens morphology from E15.5d to P8w. Western blot analysis was performed to confirm the previous proteomics results.

Results: : The Hsf4-null mice presented abnormal phenotype of the lens since E15.5d, and cataract formation at P1d. As revealed by morphological analysis, the number of epithelial nuclei of the Hsf4-null mice in the equatorial region was more than wide type mice. Lens fiber elongation became insufficient and reached only short distance from the equator. The down-regulated B crystalline expression level was confirmed by western bolt.

Conclusions: : The morphological changes of the lens of Hsf4-null mice have been observed since embryonic stage. Meanwhile, the differential expression of B crystalline was also documented. The loss of HSF4 function appears to lead to a decrease in B crystalline expression. And then, abnormal lens development and cataract formation ensue.

Keywords: cataract • crystallins