Altered peripheral myelination in mice lacking GABA_B receptors

Emerging evidence implicates γ-aminobutyric acid type B (GABA_B) receptors in peripheral nervous system (PNS) functions. In order to elucidate which biochemical, morphological and functional parameters of peripheral nerve fibers depend on GABA_B receptors we studied GABA_B1-deficient mice, which are devoid of functional GABA_B receptors. Here, we show that GABA_B1-deficient mice exhibit morphological and molecular changes in peripheral myelin, including an increase in the number of irregular fibers and increases in the expression levels of the myelin proteins PMP22 and P0. Moreover, the number of small myelinated fibers and small neurons of the lumbar dorsal root ganglia is higher in GABA_B1-deficient mice than in wild-type littermates. We further show that GABA_B1-deficient mice exhibit gait alterations and reduced allodynia. In summary, our findings implicate GABA_B receptors in the PNS myelination process and raise the possibility that PNS alterations contribute to the sensory phenotypes of GABA_B1-deficient mice.