Effects Of Skin Specific Knockout Ppp2ca Gene On Hair Growth In Mice

Background and Objective:Protein phosphorylation and dephosphorylation plays a very important role in cell activity. Protein phosphatase2A (PP2A) in mammals is the major serine/threonine phosphatases involved in cellular metabolism, DNA replication, cell differentiation and cell cycle activities. Recent research shows that PP2A also involves in the proliferation and differentiation of skin cells, and wound healing. The research intends to research the function of Ppp2ca in the development of skin by the inactivation of Ppp2ca (C subunit of PP2A) in mice keratinocytes.Method:To get the mutant mice with Ppp2ca deletion as early as in keratinocytes at E14.5, the Kre14-Cre transgenic mice were crossed with Ppp2ca Conditional knockout mice through two generations. The impact of Ppp2ca deficient in skin keratinocytes was assessed by performing the periodical assays of western, slices of skin and immunohistochemistry experiment etc.Results:Firstly the mice with the genotype of Ppp2caflox/flox; Krtl4-Cre were obtained successfully. The knockout efficiency of Ppp2ca was assessed by skin genomic gene PCR and western blotting. The results showed lower Ppp2ca expression. The knockout mice which lost Ppp2ca specific in keratinocytes exhibited apparent smaller weight, sparse hair and pigmentation sole.30%knockout mice died within6W after birth. Different developmental stages tissue sections including (follicular morphogenesis) P5,(anagen) P11,(catagen) P17,(telogen) P24and (anagen) P32were detected for histological. These knockout mice showed abnormal hair follicle morphogenesis from the first postmatal hair cycle. The hair follicle morphogenesis of the knockout mice was disorganized, hair bulbs couldn’t well-descended into the fat layer of the skin and the process of hair growth was arrested, all of which suggested Ppp2ca was required in hair growth. Protein keratin14and Ppp2ca were detected in the keratinocytes by immunohistochemistry. Decreased expression of hair follicle differentiation markers AE13and AE15were detected skin sections of mice lacking Ppp2ca. The results indicated that the expression of hair-shaft cortex keratin and trichohyalin granular proteins in the medulla of the hair shaft and the IRS were significantly reduced. All of these demonstrated the abnormal hair follicle differentiation.Conclusion:This research confirmed that mice lacking Ppp2ca in skin keratinocytes lead to handicap in development, smaller size and pigmentation sole, abnomal differentiation of hair follicle and sparse hair. We speculated that Ppp2ca might involve in the hair follicle differentiation singling pathways and was an essential gene in hair growth.