Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice

Voskuhl, Rhonda R.; Pribýl, T; Kampf, Kathy; Handley, Vance; Liu, Hong-biao; Feng, Ji‐Ming; Campagnoni, Celia W.; Soldan, Samantha S.; Messing, Albee; Campagnoni, Anthony T.

doi:10.1016/s0165-5728(03)00161-9

Cited by 14 publications

(10 citation statements)

References 25 publications

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“…These golli KO mice have a complex phenotype reflecting the loss of golli expression in the two major systems in which they are expressed (i.e., the immune and nervous systems) and the cell types in which they are expressed within each system. Ablation of golli expression causes abnormalities in the immune system and its response to experimental autoimmune encephalomyelitis (Voskuhl et al, 2003). We have reported, in preliminary form, that the KO animals exhibit behavioral abnormalities (Olmstead et al, 2000) reflective of neuronal abnormalities, and we report here effects of the ablation of the golli products on OLs and myelination in selected regions of the brain.…”

Section: Introductionmentioning

confidence: 49%

Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene

Jacobs

Pribýl²,

Feng³

et al. 2005

J. Neurosci.

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The myelin basic protein (MBP) gene encodes two families of proteins, the classic MBP constituents of myelin and the golli-MBPs, the function of which is less well understood. In this study, targeted ablation of the golli-MBPs, but not the classic MBPs, resulted in a distinct phenotype unlike that of knock-outs (KOs) of the classic MBPs or other myelin proteins. Although the golli KO animals did not display an overt dysmyelinating phenotype, they did exhibit delayed and/or hypomyelination in selected areas of the brain, such as the visual cortex and the optic nerve, as determined by Northern and Western blots and immunohistochemical analysis with myelin protein markers. Hypomyelination in some areas, such as the visual cortex, persisted into adulthood. Ultrastructural analysis of the KOs confirmed both the delay and hypomyelination and revealed abnormalities in myelin structure and in some oligodendrocytes. Abnormal visual-evoked potentials indicated that the hypomyelination in the visual cortex had functional consequences in the golli KO brain. Evidence that the abnormal myelination in these animals was a consequence of intrinsic problems with the oligodendrocyte was indicated by an impaired ability of oligodendrocytes to form myelin sheets in culture and by the presence of abnormal Ca 2ϩ transients in purified cortical oligodendrocytes studied in vitro. The Ca 2ϩ results reported in this study complement previous results implicating golli proteins in modulating intracellular signaling in T-cells. Together, all these findings suggest a role for golli proteins in oligodendrocyte differentiation, migration, and/or myelin elaboration in the brain.

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Section: Introductionmentioning

confidence: 49%

Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene

Jacobs

Pribýl²,

Feng³

et al. 2005

J. Neurosci.

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“…Based on the observations that golli protein and other myelin proteins (such as PLP) are synthesized de novo in immune tissues, Voskuhl proposed that the epitope-spreading during EAE may not occur in CNS but rather within lymphoid tissues [5]. Supporting this idea, they found that golli expression is increased in lymph nodes of mice with relapsing EAE [11], and that heterozygous golli knockout SJL mice show reduced relapse rates [12].…”

Section: Golli Proteins As Myelin-related Self-antigensmentioning

confidence: 99%

“…The shared MBP epitopes in golli protein have initiated a series of studies [5,7,8,[11][12][13][14][15][16] on its potential role as a myelin self-antigen to induce tolerance. However, studies using MBP 1-11 -specific TCR transgenic mice [26,27] indicate that the presence of golli proteins in the thymus does not induce clonal deletion of the MBP 1-11 -specific T-cells, although this classic MBP 1-11 sequence is found within golli proteins.…”

Section: Golli Proteins Regulate T-cell Activationmentioning

confidence: 99%

Minireview: Expression and Function of Golli Protein in Immune System

Feng¹

2006

Neurochem Res

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“…To explore this further, we generated golli-deficient mice by ablating exon 2 of the mbp gene (Voskuhl et al, 2003;Jacobs et al, 2005), which includes the translation initiation site for the golli proteins. In these mice, the amounts of classic MBPs in brain were not affected by the golli ablation.…”

Section: Introductionmentioning

confidence: 99%

Golli Protein Negatively Regulates Store Depletion-Induced Calcium Influx in T Cells

Feng¹,

Hu²,

Xie

et al. 2006

Immunity

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Calcium influx is crucial for T cell activation and differentiation. The detailed regulation of this process remains unclear. We report here that golli protein, an alternatively spliced product of the myelin basic protein gene, plays a critical role in regulating calcium influx in T cells. Golli-deficient T cells were hyperproliferative and showed enhanced calcium entry upon T cell receptor stimulation. We further found that golli regulates calcium influx in T cells through the inhibition of the store depletion-induced calcium influx. Mutation of the myristoylation site on golli disrupted its association with the plasma membrane and reversed its inhibitory action on Ca2+ influx, indicating that membrane association of golli was essential for its inhibitory action. These results indicate that golli functions in a unique way to regulate T cell activation through a mechanism involving the modulation of the calcium homeostasis.

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Experimental autoimmune encephalomyelitis relapses are reduced in heterozygous golli MBP knockout mice

Cited by 14 publications

References 25 publications

Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene

Region-Specific Myelin Pathology in Mice Lacking the Golli Products of the Myelin Basic Protein Gene

Minireview: Expression and Function of Golli Protein in Immune System

Golli Protein Negatively Regulates Store Depletion-Induced Calcium Influx in T Cells

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