A Newly Identified Spliceosomal Protein AHED Is Essential for Homeostasis of the Epidermis

Abstract

To identify genes that are essential for the functions of cells and organs, we established a homozygous mutant mouse embryonic stem cell bank from which we identified a gene, Ahed, that plays an essential role in hematopoiesis. In this study, we characterized the role of AHED in the skin by analyzing mice with an epidermis-specific Ahed deficiency. Those mice had apoptotic cells in their epidermis from the perinatal stage. Thereafter, they developed skin barrier disruptions over time, which caused lethality soon after birth. Experiments using inducible Ahed deletion in vivo and in vitro revealed that an Ahed deficiency led to keratinocyte apoptosis, impaired keratinocyte proliferation, and promoted dermatitis development. Because we found that AHED is a nuclear protein, we further revealed that AHED interacts with known spliceosomal proteins in HeLa cells. Moreover, altered splicing mRNA patterns were demonstrated in Ahed-deficient keratinocytes. These results suggest that AHED plays a crucial role in the maintenance of epidermal integrity, and more importantly, it contributes to mRNA splicing that is essential for multiple cell lineages.