Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance

The adhesive cell surface molecule P-0 is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin forma tion and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P-0 (P-0(+/ -) mice), an established animal model for a subtype of hereditary neuropath ies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bre d P-0(+/-) mice with null mutants for the recombination activating gene 1 ( RAG-1) or with mice deficient in the T-cell receptor alpha-subunit. We foun d that in P-0(+/-) mice myelin degeneration and impairment of nerve conduct ion properties is less severe when the immune system is deficient. Moreover , isolated T-lymphocytes from P-0(+/-) mice show enhanced reactivity to mye lin components of the peripheral nerve, such as P-0, P-2, and myelin basic protein. We hypothesize that autoreactive immune cells can significantly fo ster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.