Transgenic mice with selective knock-out of CD44 in keratinocytes display defective mitogen-induced keratinocyte proliferation and delayed hair regrowth

CD44 is a multifunctional transmembrane glycoprotein which acts as the principal cell-surface receptor for hyaluronate in different cell types. Interaction of CD44 with hyaluronate plays an important role in several physiologic processes such as cell adhesion, migration, activation and proliferation, and hyaluronate uptake and degradation, however, the biologic role of CD44 in vivo in various tissues remains to be elucidated. In our previous study, in order to determine the function of CD44 in the skin we have developed transgenic mice with a keratinocyte-specific CD44 expression defect. Analysis of these mice has shown that loss of CD44 expression leads to a defect in keratinocyte proliferation in vivo and in vitro and to an abrogation in tissue repair and carcinogen-induced epidermal hyperplasia. In this study we further analyzed in vivo keratinocyte proliferation in these mice in response to a mitogen, tetradecanoylphorbolacerate, and to hair plucking. Our results show that absence of CD44 impairs the keratinocyte proliferation in both conditions and consequently causes a delay in hair regrowth. These observations support our previous results and provide complementary evidence for the concept that CD44 is implicated in the regulation of keratinocyte proliferation induced by a variety of extracellular stimuli in the skin.