Whn and mHa3 are components of the genetic hierarchy controlling hair follicle differentiation

The molecular basis of the characteristic hair growth disorder in nude mice that carry a defective Whn transcription factor gene is unknown. A comparison of mRNA populations from wild-type and nude mice back skin by representational difference analysis revealed the absence of acidic hair keratin gene 3 (mHa3) mRNA in mutant mice. Whn and acidic hair keratin genes are co-expressed in hair follicles, nail forming regions and filiform papillae of the tongue: expression of the mHa3 gene is generally detectable about 1 day after Whn mRNA and rapidly ceases in its absence. Whn is strongly expressed during the anagen (growth) phase of the hair cycle in matrix, cortex and outer root sheath; its expression rapidly declines during catagen and is undetectable in telogen phases. In nude mice, low levels of mHa3 expression are maintained in nails and whisker follicles, whereas expression is completely absent in pelage hair follicles and filiform papillae. Thus, the nude phenotype represents the first example of an inherited skin disorder that is associated with the loss of expression rather than structural mutation of keratin genes. The distinct molecular difference between pelage and whisker follicles correlates with the improved mechanical stability of vibrissae in nude mice, implicating mHa3 as an important structural component of the hair shaft.