Abnormal cochlea linked to deafness in transgenic mice expressing human cytokeratin K8

Abstract

The cytokeratin intermediate filaments have a relevant role in the proliferation and differentiation processes of epithelial cells. To provide information about the role of K8 cytokeratin during the auditory receptor differentiation, two groups of adult mice were used: TGK8-4 transgenic and control animals. The TGK8-4 transgenic mice contained 12 kb of K8 human cytokeratin (HK8) locus (Casanova et al., 1995, 1999). The functional activity of the auditory receptor was analyzed by auditory thresholds. Morphological studies demonstrate that the auditory receptors of the TGK8-4 transgenic mice are highly immature. Immunocytochemical studies were made by using two monoclonal antibodies: CAM 5-2 (recognizing K8 human cytokeratin) and Troma-1 (recognizing both mouse and human K8 cytokeratin). These demonstrated significant differences between the auditory receptors of the transgenic mice and the control mice. These functional and morphological differences clearly suggest that K8 cytokeratin has a relevant role during the differentiation and tridimensional organization of the sensory and the supporting cells of the auditory receptor.