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. Here, we investigated whether Ahed also plays a critical role in proliferation and / or differentiation of epidermal keratinocytes, similar to in hematopoietic cells.
To the end we generated epidermal-specific Ahed deficient (Ahed EcKO) mice by crossing Ahed flox mice with K5.Cre mice. The Ahed EcKO were clearly distinguishable from control littermates by growth retardation, thinning of the skin at postnatal day 2 (P2) and lethality around P3. The Ahed EcKO 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 unavailability of the experimental materials due to neonatal lethality, tamoxifen inducible KO (Ahed IndEcKO) mice were newly generated by crossing Ahed flox mice with K5-CreERT2 mice. The Ahed IndEcKO mice showed atrophic epidermis and cell death in hair follicles by topical treatment with high dose 4-OH Tamoxifen (4OHT) at day10. In contrast to this, eczematous skin lesions were developed with low dose 4OHT at later period. TUNEL staining revealed apoptotic cells in interfollicular and follicular epidermis and the TUNEL positive cells were increased in dose-dependent manner. 
Primary culture of epidermal keratinocytes from the Ahed IndEcKO mice demonstrated significant deficiency of the cell proliferation by 4OHT treatment for in vitro KO. Flowcytometric analysis revealed increased G2/M population of the 4OHT treated keratinocytes.
Collectively, the data suggests crucial roles of Ahed in development and maintenance of epidermis, similar to those of hematopoietic cells.

Ahed plays crucial roles in growth and differentiation of epidermal keratinocytes