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Optic nerve alterations in P27(Kip1) knockout mice
E Lopez-Sanchez1, E Frances-Muñoz, V Chaques
1Hospital Arnau de Vilanova, Valencia, Spain. elopez@comv.es
Purpose:
To study the morphologic characteristics of the optic nerve (ON) by using an experimental model of knockout mice for the expression of the P27(Kip1) gene, mainly involved in cell cycle arrest, apoptosis control, and retinoblastoma protein phosphorylation.
Methods:
Eyeballs with the retrobulbar ON attached were obtained from 26-week-old mice. By using morphologic and morphometric techniques, light and electron transmission microscopy, the ON characteristics were determined in two groups of mice: 1) wild type mice as the control group (n=15), 2) homozygous knockout mice (-/-) for the P27(Kip1) gene as the knockout group (n=15). Glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) were studied using Western blot and immunoblotting approaches.
Results:
The ON cross-sectional area was significantly larger in the P27(Kip1) knockout mice group than in the control group (p<0.001). The axon sizes in knockout animals were much larger than in wild-type mice (p<0.001). Higher number of axons forming the ON, intra-axonal degeneration, myelin sheath, and axoplasm density alterations were found in P27(Kip1) knockout mice when compared with control group (p<0.001). Analysis of lysates of optic nerves by Western blot showed less expression of myelin basic protein and GFAP in P27(Kip1) knockout mice as compared to wild type mice (p<0.005, p<0.01, respectively).
Conclusions:
The morphologic and morphometric results suggest that homozygous P27(Kip1) knock-out mice had hypertrophic, hyperplastic, and dystrophic ON.
Insights
P27(Kip1) gene knockout mice exhibit significantly larger optic nerves with altered axon size and density. These findings suggest hypertrophic, hyperplastic, and dystrophic optic nerves in P27(Kip1) knockout models.
Area of Science:
- Neuroscience
- Genetics
- Ophthalmology
Background:
- The P27(Kip1) gene plays a crucial role in cell cycle regulation, apoptosis, and protein phosphorylation.
- Understanding its role in optic nerve development and health is essential for neuro-ophthalmological research.
Purpose of the Study:
- To investigate the morphologic and morphometric characteristics of the optic nerve (ON) in mice lacking the P27(Kip1) gene.
- To assess the impact of P27(Kip1) gene knockout on optic nerve structure and protein expression.
Main Methods:
- Utilized morphologic and morphometric techniques, including light and electron transmission microscopy, on optic nerves from P27(Kip1) knockout and wild-type mice.
- Analyzed glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) expression using Western blot and immunoblotting.
Main Results:
- P27(Kip1) knockout mice showed a significantly larger ON cross-sectional area and larger axon sizes compared to controls (p<0.001).
- Increased axon numbers, intra-axonal degeneration, and alterations in myelin sheath and axoplasm density were observed in knockout mice (p<0.001).
- Reduced expression of MBP and GFAP was detected in the optic nerves of P27(Kip1) knockout mice (p<0.005, p<0.01).
Conclusions:
- Homozygous P27(Kip1) knockout mice present with hypertrophic, hyperplastic, and dystrophic optic nerves.
- These findings highlight the critical role of P27(Kip1) in regulating optic nerve morphology and cellular integrity.
