ORGANIZATION AND EXPRESSION OF HAIR FOLLICLE GENES

Several families of proteins are expressed in the growth of hair and a n estimated 50 - 100 proteins constitute the final hair fiber. The cum bersome nomenclature for naming these different proteins has led to a proposal to modify that which is currently used for epidermal keratins . Investigations of the organization of hair genes indicate that the m embers of each family are clustered in the genome and their expression could be under some general control. Interestingly, the protein calle d trichohyalin, markedly distinct from the hair proteins, is produced in the inner root sheath cells and the gene for it has been found to b e located at the same human chromosome locus as the genes for profilag grin, involucrin, and loricrin. A mainstream objective is to identify controls responsible for the production in the hair cortex of keratin intermediate filaments (IFs) and two large groups of keratin-associate d proteins (KAPs) rich in the amino acids cysteine or glycine/tyrosine . A specific family of cysteine-rich proteins is expressed in the hair cuticle. Comparisons of promoter regions of IF genes and KAP genes, i ncluding a recently characterized gene for a glycine/tyrosine-rich pro tein, have revealed putative hair-specific motifs in addition to known elements that regulate gene expression. In the sheep, the patterns of expression in hair differention are particularly interesting insofar as there are distinct segments of para- and orthocortical type cells t hat have significantly different pathways of expression. The testing o f candidate hair-specific regulatory sequences by mouse transgenesis h as produced several interesting hair phenotypes. Transgenic sheep over -expressing keratin genes but showing no hair growth change have been obtained and compared with the equivalent transgenic hair-loss mice. S tudies of the effects of amino acid supply on the rate of hair growth have demonstrated that with cysteine supplementation of sheep a pertur bation occurs in which there is a markedly increased level of only one type of mRNA and the ration of para- to orthocortical cells is increa sed. A molecular explanation of this phenomenon is being sought.