CHARACTERIZATION OF BSK MICE - I - THE BSK MUTATION DOES NOT INVOLVE A RECOMBINATION OF CORNEA-SPECIFIC KERATIN 12 AND SKIN-SPECIFIC HAIR KERATIN GENES

Purpose. Bsk (bare skin) is an autosomal dominant mutation linked to t he Krt 1 (type 1 keratin) locus of mouse chromosome 11. The adult Bsk mouse manifests hair loss and corneal opacity. To identify and charact erize the keratin genes involved in this mutation, we examined the hyp othesis proposing that the Bsk mutation might involve a recombination event between cornea-specific (K12) and hair-specific (mHa 1, 2, 3 and 4) type I keratin genes. Methods. The Bsk phenotype was examined by h istochemical analysis, using light and electron microscopy. RFLP was u sed for their genotyping, and possible keratin gene expression was exa mined by immunohistochemical staining, Western analysis, RT-PCR and No rthern hybridization. Results. Northern hybridization, RT-PCR and West ern blot analysis revealed that mHa 1, 2, 3 and 4 keratins are express ed in the skin, but not in cornea, whereas the expression of K12 is li mited to the corneas of the Bsk mice. These data ruled out the hypothe sis that Bsk phenotype results from a recombination event between K12 and mHa 1, 2, 3 and 4. Ultrastructural and biochemical analyses also i ndicated that Bsk does not involve negative dominant mutations of kera tin 12, mHa 1, 2, 3 and 4, epidermal-specific keratin 10, or basal cel l-specific keratin 14. Expression of an acidic 50 kD keratin, recogniz ed by monoclonal antibody AK 2, was up-regulated in the injured cornea s of normal mice as well as Bsk corneas. Conclusion. The gene linked t o the Bsk mutation remains unknown. The pathological changes in the sk in and corneas may be secondary to the loss of protecting hairs and la shes by an unknown mechanism.