Effects of the jimpy mutation on mouse retinal structure and function

Abstract

The Jimpy mutant mouse has a point mutation in the proteolipid protein gene (plp1). The resulting misfolding of the protein leads to oligodendrocyte death, myelin destruction, and failure to produce adequately myelinated axons in the central nervous system (CNS). It is not known how the absence of normal myelination during development influences neural function. We characterized the Jimpy mouse retina to find out whether lack of myelination in the optic nerve during development has an effect on normal functioning and morphology of the retina. Optokinetic reflex measurements showed that Jimpy mice had, in general, a functional visual system. Both PLP1 antibody staining and reverse transcriptase-polymerase chain reaction for plp1 mRNA showed that plp1 is not expressed in the wild-type retina. However, in the optic nerve, plp1 is normally expressed, and consequently, in Jimpy mutant mice, myelination of axons in the optic nerve was mostly absent. Nevertheless, neither axon count nor axon ultrastructure in the optic nerve was affected. Physiological recordings of ganglion cell activity using microelectrode arrays revealed a decrease of stimulus-evoked activity at mesopic light levels. Morphological analysis of the retina did not show any significant differences in the gross morphology, such as thickness of retinal layers or cell number in the inner and outer nuclear layer. The cell bodies in the inner nuclear layer, however, were larger in the peripheral retina of Jimpy mutant mice. Antibody labeling against cell type-specific markers showed that the number of rod bipolar and horizontal cells was increased in Jimpy mice. In conclusion, whereas the Jimpy mutation has dramatic effects on the myelination of retinal ganglion cell axons, it has moderate effects on retinal morphology and function.

Assessment of the Retina of Plp-α-Syn Mice as a Model for Studying Synuclein-Dependent Diseases

“…In line with previous reports, 54,55 we did not detect Plp immunoreactivity in the retinas of wild-type and Plp-α-Syn mice (Fig. 5A).…”

“…Although the retina is devoid of oligodendroglia cells and Plp protein, 54,55 we observed human α-Syn protein in the retina. Our western blot experiments supported the presence of human α-Syn in the retina.…”

Modeling the Chronic Loss of Optic Nerve Axons and the Effects on the Retinal Nerve Fiber Layer Structure in Primary Disorder of Myelin

“…A recent study on the retina of a murine model of PMD (the jimpy mouse) showed that the structure of the retina is normal at 22 days of age despite severe dysmyelination of the optic nerve though no loss of axons. 55 The optic nerves in the shp show a clear loss of axons that appears to increase in time. The earliest evidence of axon degeneration was noted at 4 months, though notable areas of axon loss and gliosis were not apparent until much later (two or more years).…”