Expression from another K6 gene (yellow) explains hair growth in double knockout mice.

By knocking out the two known keratin 6 (K6) genes in mice, Wojcik et al. (page 619) have discovered a third murine K6 gene, and simultaneously created a promising model system for studying keratin function in more detail. In an effort to study the function of K6, the authors generated a mouse line lacking both K6a and K6b, and found that plaques develop on the tongues of these mice and cause the majority to die of starvation within two weeks of birth. Surprisingly, and in contrast to a previously described mouse K6a/b knockout line, ∼25% of the mice survive to adulthood and grow normal hair and nails. Further analysis uncovered a previously undescribed murine K6 gene, an ortholog of the K6hf gene from human hair follicles, which the authors have named MK6hf.

While the presence of MK6hf helps explain why the knockout mice develop normal hair and nails, some mysteries remain. MK6hf is not expressed in oral epithelia, and all of the mice exhibit ultrastructural abnormalities in their tongues, so it is unclear why some survive to adulthood while others die. Wojcik and colleagues are now performing backcrosses to search for unknown genetic modifiers involved in epithelial integrity.

The results also suggest that inducible K6 expression may be less important in wound healing than was previously believed, since the knockout mice heal wounds normally. Rather than helping in the initial events of wound healing such as proliferation and migration, keratins may be induced to strengthen the tissue once it has been repaired. ▪