Thus in NMO, since the interaction of NMO-IgG and AQP4 leads to a functional knockout phenotype of AQP4, edema develops as a result of functional impairment of AQP4 although BBB is expected to be still intact, which may explain the paradoxical lack of gadolinium enhancement in most NMO lesions. The gene discussed is AQP4; the disease is neuromyelitis optica.