Although the hairless phenotype was first observed in the mouse 75 years ago and both the mouse and human hairless genes have been cloned, the function of the Hairless protein has, until now, remained a mystery.
As published in Genes & Development, Dr. Catherine C. Thompson and colleagues at the Kennedy Krieger Research Institute and Johns Hopkins School of Medicine have determined the function of the Hairless protein: Hairless is a protein that works together with the thyroid hormone receptor. In the absence of thyroid hormone, the Hairless protein acts in concert with the thyroid hormone receptor to recruit the necessary factors to turn off gene expression that is dependent upon the receptor. Depending upon the type and severity of the mutation in the hairless gene, the Hairless protein is unable to fulfill its normal role in this pathway, and the phenotypic consequences range from patchy to complete hair loss.
The discovery that Hairless mediates thyroid hormone receptor-dependent gene repression provides the first molecular insight into the role of Hairless in congenital hair loss disorders. This discovery represents a stepping stone upon which researchers can further delineate the genetic pathway of hair loss, and eventually design therapeutic agents.