Maintenance mechanism of epidermal homeostasis and its failure- Functional analysis of MCL1 in keratinocyte differentiation-

Research Project

Project/Area Number	26461669
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Dermatology
Research Institution	Kawasaki Medical School
Principal Investigator	MAKINO EIICHI 川崎医科大学, 医学部, 講師 (90314674)
Project Period (FY)	2014-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	MCL1 / 表皮角化細胞 / 分化 / ホメオスタシス / アポトーシス
Outline of Final Research Achievements	We successfully generated two kinds of MCL1 conditional knockout (cKO) mice, K5-Cre: MCL1flox / flox mouse and K14-CreERT2: MCL1flox / flox mouse.In these mice, Cre recombinase was induced using the tissue specific promoters of keratin 5 (K5) and keratin 14 (K14) ,which were strongly expressed in epidermal basal cells, and as a result, the flox allele of MCL1 is missing. In the MCL1 cKO mouse, marked hyperkeratosis and epidermal hyperplasia were observed in the skin as compared with the control mouse, but clear findings of apoptosis were not obtained.Immunostaining of MCL1 revealed that MCL1 expression was maximal in the stratum corneum in normal skin tissues and MCL1 expression was not observed in the basal layer. Interestingly, these results suggest that MCL1 may exert some function in the terminal differentiation process of epidermal cells.