z-logo
Premium
Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin‐2
Author(s) -
MonasterioSchrader Patricia,
Patzig Julia,
Möbius Wiebke,
Barrette Benoit,
Wagner Tadzio L.,
Kusch Kathrin,
Edgar Julia M.,
Brophy Peter J.,
Werner Hauke B.
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22561
Subject(s) - tetraspanin , biology , neuroinflammation , myelin , neuroscience , degeneration (medical) , axonal degeneration , central nervous system , pathology , immunology , medicine , inflammation , biochemistry , cell
Deficiency of the major constituent of central nervous system (CNS) myelin, proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type‐2 patients and in Plp1 null ‐mice but is compatible with almost normal myelination. These observations led us to speculate that PLP's role in myelination may be partly compensated for by other tetraspan proteins. Here, we demonstrate that the abundance of the structurally related tetraspanin‐2 (TSPAN2) is highly increased in CNS myelin of Plp1 null ‐mice. Unexpectedly, Tspan2 null ‐mutant mice generated by homologous recombination in embryonic stem cells displayed low‐grade activation of astrocytes and microglia in white matter tracts while they were fully myelinated and showed no signs of axonal degeneration. To determine overlapping functions of TSPAN2 and PLP, Tspan2 null * Plp1 null double‐mutant mice were generated. Strikingly, the activation of astrocytes and microglia was strongly enhanced in Tspan2 null * Plp1 null double‐mutants compared with either single‐mutant, but the levels of dysmyelination and axonal degeneration were not increased. In this model, glial activation is thus unlikely to be caused by axonal pathology, and vice versa does not potentiate axonal degeneration. Our results support the concept that multiple myelin proteins have distinct roles in the long‐term preservation of a healthy CNS, rather than in myelination per se . GLIA 2013;61:1832–1847

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here