GENE TARGETING OF BPAG1 - ABNORMALITIES IN MECHANICAL STRENGTH AND CELL-MIGRATION IN STRATIFIED EPITHELIA AND NEUROLOGIC DEGENERATION

BPAG1 is the major antigenic determinant of autoimmune sera of bullous pemphigoid (BP) patients. It is made by stratified squamous epithelia , where it localizes to the inner surface of specialized integrin-medi ated adherens junctions (hemidesmosomes). To explore the function of B PAG1 iind its relation to BP, we targeted the removal of the BPAG1 gen e in mice. Hemidesmosomes are otherwise normal, but they lack the inne r plate and have no cytoskeleton attached. Though not affecting cell g rowth or substratum adhesion, this compromises mechanical integrity an d influences migration. Unexpectedly, the mice also develop severe dys tonia and sensory nerve degeneration typical of dystonia musculorum (d t/dt) mice. We show that in at least one other strain of dt/dt mice, B PAG1 gene is defective.