Generation of filggrin-deficient mice and analysis o differentiation and apoptosis of keratinocytes

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It has been reported that filaggrin may be involved in the terminal differentiation (apoptosis) of keratinocytes. In order to study of keratinocyte differentiation in vivo, we are planning to generate filaggrin-deficient mice. Filaggrin is composed of approximately 320 amino acids and the unit of profilaggrin, which consists of multiple filaggrin-repeats. To generate filaggrin-deficient mice, we need to disrupt the region containing the initiation codon of the profilaggrin gene rather than the coding region of filaggrin. We succeeded to obtain a BAC clone containing the mouse profilaggrin gene with a human profilaggrin cDNA as a probe. We have subloned the important regions of this gene to design a targeting vector. At present, filaggrin^<+/-> ES cells are under construction.