TARGETED EXPRESSION OF A DOMINANT-NEGATIVE FGF RECEPTOR MUTANT IN THEEPIDERMIS OF TRANSGENIC MICE REVEALS A ROLE OF FGF IN KERATINOCYTE ORGANIZATION AND DIFFERENTIATION

In this study we used a dominant-negative FGF receptor mutant to block FGF function in a specific tissue of transgenic mice. The mutant rece ptor, which is known to block signal transduction in celts when co-exp ressed with wild-type receptors, was targeted to suprabasal keratinocy tes using a keratin 10 promoter. The transgene was expressed specifica lly in the skin and highest expression levels were found in the tail. Expression of the mutant receptor disrupted the organization of epider mal keratinocytes, induced epidermal hyperthickening and resulted in a n aberrant expression of keratin 6. This suggests that FGF is essentia l for the morphogenesis of suprabasal keratinocytes and for the establ ishment of the normal program of keratinocyte differentiation. Our stu dy demonstrates that dominant-negative growth factor receptors can be used to block selectively the action of a growth factor in specific ti ssues of transgenic mice.