Ahed plays crucial roles in homeostatic maintenance of epidermis

Ahed (attenuated hematopoietic development) is a newly identified gene based on in vitro screening assay of the homozygous mutant mouse embryonic stem cell bank, and found to be essential for hematopoiesis. Mice with Ahed deletion in the hematopoietic lineage showed fetal anemia due to impairment in proliferation of differentiated blood cells.Here, we investigated whether Ahed also plays a critical role in proliferation and / or differentiation of epidermal keratinocytes. To the end we generated epidermal-specific Ahed deficient mice by crossing Ahed flox and K5.Cre mice. Ahed conditional knockout (Ahed cKO) mice showed no significant abnormality at birth. However, Ahed cKO mice were clearly distinguishable from control littermates by growth retardation, thinning of the skin at postnatal day 2 (P2) and lethality around P3. Ahed cKO mice showed a marked increase of transepidermal water loss at P2, indicative of barrier disruption. Histopathological study of their skin revealed loss of granular layer, a marked hyperkeratosis, compromised anagen follicles, and infiltration of inflammatory cells in the upper dermis. To overcome neonatal lethality, we generated inducible-Ahed KO mice by crossing K5.CreERT2 mice carrying a transgene with tamoxifen inducible Cre recombinase under the K5 promoter. The KO mice showed atrophic epidermis and cell death in hair follicles by topical treatment of high dose 4-OH Tamoxifen (Tam) at day10. In contrast, the exposure to low dose 4-OH Tam for 3 weeks led to generation of eczematous lesion. Collectively, the results suggest crucial roles of Ahed in the development and maintenance of the epidermis.