Related Experiment Video
Updated: Apr 11, 2026
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Effects of the jimpy mutation on mouse retinal structure and function
Anahit Hovhannisyan1,2, Boris Benkner1, Antje Biesemeier3
1Retinal Circuits and Optogenetics, Center for Integrative Neuroscience, University of Tübingen, 72076, Tübingen, Germany.
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.
Insights
The Jimpy mouse, with a mutation affecting proteolipid protein (PLP1), shows reduced myelination in the optic nerve. This impacts retinal ganglion cell function, particularly at lower light levels, but has minimal effects on overall retinal structure.
Area of Science:
- Neuroscience
- Genetics
- Ophthalmology
Background:
- The Jimpy mouse model exhibits a point mutation in the proteolipid protein gene (plp1).
- This mutation causes protein misfolding, leading to oligodendrocyte death and myelin destruction in the central nervous system (CNS).
- The impact of developmental hypomyelination on neural function, particularly in the retina, remains largely uncharacterized.
Purpose of the Study:
- To investigate the effects of absent optic nerve myelination during development on retinal morphology and function in Jimpy mutant mice.
- To assess visual system function using optokinetic reflex measurements.
- To analyze retinal cellular structure and ganglion cell activity.
Main Methods:
- Optokinetic reflex testing to evaluate visual function.
- PLP1 antibody staining and reverse transcriptase-polymerase chain reaction (RT-PCR) to assess plp1 expression and myelination.
- Microelectrode array recordings to measure retinal ganglion cell activity.
- Morphological analysis including axon counting, ultrastructure, and retinal layer thickness.
- Immunohistochemistry using cell type-specific markers.
Main Results:
- Jimpy mice possess a generally functional visual system, despite significant hypomyelination of the optic nerve axons.
- No significant changes were observed in optic nerve axon count or ultrastructure.
- Reduced stimulus-evoked activity in retinal ganglion cells was detected at mesopic light levels.
- Retinal morphology was largely unaffected, though some cell types (rod bipolar and horizontal cells) showed increased numbers in the inner nuclear layer.
Conclusions:
- The Jimpy mutation severely impairs myelination of retinal ganglion cell axons.
- Despite significant myelination deficits in the optic nerve, retinal function is moderately affected, with notable changes in ganglion cell activity under specific light conditions.
- The study highlights a complex relationship between optic nerve myelination and retinal function, with some compensatory mechanisms potentially at play.
