immune cells/T-lymphocyte research - from Germany

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Abstract from Brain 2003 Apr;126(Pt 4):804-13

Preserved myelin integrity and reduced axonopathy in

connexin32-deficient mice lacking the recombination activating gene-1.

Kobsar I, Berghoff M, Samsam M, Wessig C, Maurer M, Toyka KV, i R.

Department of Neurology, University of Wurzburg, Wurzburg, Germany.

Mice heterozygously deficient for myelin protein zero (P0) mimicking

human Charcot-Marie-Tooth (CMT) disease 1B show T-lymphocyte and

macrophage upregulation in peripheral nerves, which aggravates and

modulates the genetically mediated demyelinating neuropathy. In

connexin32 (cx32)-deficient (cx32(def)) mice, which mimic the X-linked

dominant form of CMT (CMTX), T-lymphocyte and macrophage numbers are

also significantly elevated in peripheral nerves. To test the hypothesis

that immune cells are indeed pathogenic in this model, we cross-bred

cx32(def) mice with recombination activating gene-1 (RAG-1)-deficient

mice, which lack mature T- and B-lymphocytes. In these immunoincompetent

double mutants, the number of endoneurial macrophages was reduced.

Furthermore, features indicative of myelin degeneration and axonopathic

changes were mitigated in the RAG-1-deficient double mutants, whereas

enlarged periaxonal Schwann cell collars, a hallmark specific for

cx32-mutants, were not reduced. Since both cx32- and P0 deficiency lead

to similar immunopathogenic

processes, we conclude that immune-mediated demyelination may be a

feature common to many CMT-like neuropathies independent of the genetic

origin.