Mutations in the helix termination motif of mouse type I IRS keratin genes impair the assembly of keratin intermediate filament

AbstractTwo classical mouse hair coat mutations, Rex (Re) and Rex wavy coat (Rewc), are linked to the type I inner root sheath (IRS) keratin genes of chromosome 11. An N-ethyl-N-nitrosourea-induced mutation, M100573, also maps close to the type I IRS keratin genes. In this study, we demonstrate that Re and M100573 mice bear mutations in the type I IRS gene Krt25; Rewc mice bear an additional mutation in the type I IRS gene Krt27. These three mutations are located in the helix termination motif of the 2B α-helical rod domain of a type I IRS keratin protein. Immunohistological analysis revealed abnormal foam-like immunoreactivity with an antibody raised to type II IRS keratin K71 in the IRS of Re/+ mice. These results suggest that the helix termination motif is essential for the proper assembly of types I and II IRS keratin protein complexes and the formation of keratin intermediate filaments