Resistance of young gelatinase B–deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions

• DOI: 10.1172/jci6886
• Publication Date: 2008-02-19T13:41:39Z
• Authors: Bénédicte Dubois; Stefan Masure; Ursula Hurtenbach; Liesbet Paemen; Hubertine Heremans; Joost van den Oord; Raf Sciot; Thorsten Meinhardt; Günter Hämmerling; Ghislain Opdenakker; Bernd Arnold
• Keywords: Gelatinase A; Encephalomyelitis

Regulated expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) plays a role in various physiological processes. To determine vivo how unbalanced these factors can promote or affect the course pathologies, we knocked out mouse gelatinase B gene by replacing catalytic zinc-binding domains with an antisense-oriented neomycin resistance gene. Adult B–deficient mice wild-type controls could be induced to develop experimental autoimmune encephalomyelitis (EAE) similar scores for neurologic disease, blood-brain barrier permeability, central nervous system histopathology. However, whereas diseased control animals showed necrotizing tail lesions hyperplasia osteocartilaginous tissue, adult were resistant this pathology. Gelatinase younger than 4 weeks age significantly less susceptible development EAE matched and, even as they aged, remained lesions. These data illustrate that immune that, ontogenesis, propensity autoimmunity is altered absence MMP.