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![Expression and localization of MBP and PLP1 in the retina and optic nerve. A: Maximum intensity projection of MBP and DAPI staining in wild-type mouse. Red arrows: lumina of optic nerve. B: Maximum intensity projection of PLP1 and DAPI staining in wild-type mouse. Red arrows: lumina of optic nerve. The cartoon illustrates the layout of the retina-optic nerve preparation, for A and B. C: plp1 gene expression in mouse retina and optic nerve. RT-PCR on total RNA. plp1 gene is expressed in Jimpy mutant ("Jimpy") and wild-type mouse optic nerves, but not in the retina. M, marker. Amplicon sizes: plp1: 350 bp and 499 bp (two different splice variants); tbp: 300 bp. D: Cartoon of the plp1 splice variants. Arrows indicate primer binding sites. Scale bar 5 200 lm in A,B. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]](profile/Anahit-Hovhannisyan-7/publication/285590204/figure/fig1/AS:613891079942145@1523374447450/Expression-and-localization-of-MBP-and-PLP1-in-the-retina-and-optic-nerve-A-Maximum.png)
Expression and localization of MBP and PLP1 in the retina and optic nerve. A: Maximum intensity projection of MBP and DAPI staining in wild-type mouse. Red arrows: lumina of optic nerve. B: Maximum intensity projection of PLP1 and DAPI staining in wild-type mouse. Red arrows: lumina of optic nerve. The cartoon illustrates the layout of the retina-optic nerve preparation, for A and B. C: plp1 gene expression in mouse retina and optic nerve. RT-PCR on total RNA. plp1 gene is expressed in Jimpy mutant ("Jimpy") and wild-type mouse optic nerves, but not in the retina. M, marker. Amplicon sizes: plp1: 350 bp and 499 bp (two different splice variants); tbp: 300 bp. D: Cartoon of the plp1 splice variants. Arrows indicate primer binding sites. Scale bar 5 200 lm in A,B. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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... Axonal diameters are reduced [20], whereas there is astroglial hypertrophy with an increased number of cell processes, compromising interaction with oligodendrocytes and axons [2,18,21]. In the optic nerve of 21-day-old Jimpy mice the ultrastructural appearance of axons and astrocyte cell bodies seems normal, some oligodendrocytes also look normal but others are filled with lipid inclusions, an indication of dying cells, and myelin is almost absent [22] (Fig. 2). However, impulse propagation occurs since the mice are not blind. ...
... There was also no subsequent marked decline, so in the long run (3 h) the cumulative oxygen uptake was only slightly lower that in normal littermates in a medium with 5 mM K + . Thus, at normal extracellular K + ([K + ] o ) oxidative metabolism is almost identical in Jimpy and non-Jimpy cultures, confirming the normal mitochondrial function in Jimpy mice [21,22,42], but the normal transient stimulation by excess [K + ] o is absent. ...
... Astrocytes (A) show normal morphology. From[22] ...
The Jimpy mouse illustrates the importance of interactions between astrocytes and oligodendrocytes. It has a mutation in Plp coding for proteolipid protein and DM20. Its behavior is normal at birth but from the age of ~2 weeks it shows severe convulsions associated with oligodendrocyte/myelination deficits and early death. A normally occurring increase in oxygen consumption by highly elevated K⁺ concentrations is absent in Jimpy brain slices and cultured astrocytes, reflecting that Plp at early embryonic stages affects common precursors as also shown by the ability of conditioned medium from normal astrocytes to counteract histological abnormalities. This metabolic response is now known to reflect opening of L-channels for Ca²⁺. The resulting deficiency in Ca²⁺ entry has many consequences, including lack of K⁺-stimulated glycogenolysis and release of gliotransmitter ATP. Lack of purinergic stimulation compromises oligodendrocyte survival and myelination and affects connexins and K⁺ channels. Mice lacking the oligodendrocytic connexins Cx32 and 47 show similar neurological dysfunction as Jimpy. This possibly reflects that K⁺ released by intermodal axonal Kv channels is transported underneath a loosened myelin sheath instead of reaching the extracellular space via connexin-mediated transport to oligodendrocytes, followed by release and astrocytic Na⁺,K⁺-ATPase-driven uptake with subsequent Kir4.1-facilitated release and neuronal uptake.
... Regardless of inflammation being a cause or an effect, the presence of inflammatory factor significantly complicates interpretation of the underlying mechanisms. A recent study (Hovhannisyan et al., 2015) investigated the effects of lack of myelin on neuronal function utilizing Jimpy mutant mice, in which a point mutation in the proteolipid protein gene (plp1) results in OL death and prevents normal myelination in the CNS. Although myelination of axons was absent from the optic nerve of Jimpy mice, optikinetic reflex measurements showed a functional visual system, suggesting that the lack of myelination in RGC axons had little effect on retinal function. ...
Multiple sclerosis (MS) is an autoimmune mediated neurodegenerative disease characterized by demyelination and oligodendrocyte (OL) loss in the central nervous system and accompanied by local inflammation and infiltration of peripheral immune cells. Although many risk factors and symptoms have been identified in MS, the pathology is complicated and the cause remains unknown. It is also unclear whether OL apoptosis precedes the inflammation or whether the local inflammation is the cause of OL death and demyelination. This review briefly discusses several models that have been developed to specifically ablate oligodendrocytes in an effort to separate the effects of demyelination from inflammation. © 2016, Editorial Board of Neural Regeneration Research. All rights reserved.
