Optic Nerve Alterations in PTEN<sup>+/–</sup>Mice

López-Sánchez, E.; Francés-Muñoz, Ester; Menezo, J.L.; Pinazo-Durán, María Dolores

doi:10.1177/112067210601600313

Cited by 3 publications

(3 citation statements)

References 19 publications

(23 reference statements)

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“…Moreover, the migratory and differentiation capabilities of glial progenitors are perturbed during E13 to E19 in p27 KIP1 null mice, as there were significant increases in QKI-positive; BrdU-positive cells in the subventricular zone compared to wild-type controls [42] . In addition, reduction in MBP staining is observed in p27 KIP1 knockout mice in the optic nerve, consistent with the requirement for p27 KIP1 and PNS myelination [43] . We have previously showed that p27 KIP1 increases after the ectopic expression of QKI-6/7 in oligodendrocytes [8] .…”

Section: Discussionsupporting

confidence: 74%

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

et al. 2009

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BackgroundThe quaking viable (qkv) mice have uncompacted myelin in their central and peripheral nervous system (CNS, PNS). The qk gene encodes 3 major alternatively spliced isoforms that contain unique sequence at their C-terminus dictating their cellular localization. QKI-5 is a nuclear isoform, whereas QKI-6 and QKI-7 are cytoplasmic isoforms. The qkv mice harbor an enhancer/promoter deletion that prevents the expression of isoforms QKI-6 and QKI-7 in myelinating cells resulting in a dysmyelination phenotype. It was shown that QKI regulates the differentiation of oligodendrocytes, the myelinating cells of the CNS, however, little is known about the role of the QKI proteins, or RNA binding proteins in PNS myelination.Methodology/Principal FindingsTo define the role of the QKI proteins in PNS myelination, we ectopically expressed QKI-6 and QKI-7 in primary rat Schwann cell/neuron from dorsal root ganglia cocultures. We show that the QKI isoforms blocked proliferation and promoted Schwann cell differentiation and myelination. In addition, these events were coordinated with elevated proteins levels of p27KIP1 and myelin basic protein (MBP), markers of Schwann cell differentiation. QKI-6 and QKI-7 expressing co-cultures contained myelinated fibers that had directionality and contained significantly thicker myelin, as assessed by electron microscopy. Moreover, QKI-deficient Schwann cells had reduced levels of MBP, p27KIP1 and Krox-20 mRNAs, as assessed by quantitative RT-PCR.Conclusions/SignificanceOur findings suggest that the QKI-6 and QKI-7 RNA binding proteins are positive regulators of PNS myelination and show that the QKI RNA binding proteins play a key role in Schwann cell differentiation and myelination.

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Section: Discussionsupporting

confidence: 74%

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

et al. 2009

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“…In addition, Pten -/-L7 mutant mice and Pten -/-Nse mutant mice generally exhibited appearances of thickened axonal and dendritic processes [20,25] , which was also observed in the optic nerve of Pten heterozygous mice [26] . Due to the mosaic expression of Cre recombinase, neuronal hypertrophy in these mice was restricted to neurons that showed Pten inactivation, whilst cells that retained expression exhibited normal cell morphologies, which underscores the cell-autonomous manner in which PTEN regulates cell soma size [20,21,24,25] .…”

Section: Loss Of Pten Leads To Neuronal Hypertrophymentioning

confidence: 99%

Function of PTEN during the Formation and Maintenance of Neuronal Circuits in the Brain

Diepen

Eickholt²

2007

Dev Neurosci

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PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumor suppressor that can inhibit proliferation and migration and controls apoptosis in a number of cell types, mainly through inhibition of the phosphoinositide 3-kinase (PI3K) signaling pathway. Patients carrying inactivating mutations of PTEN show a prevalence to develop tumors that can coincide with neurological defects such as mental retardation, ataxia and seizures. A number of in vitro and in vivo studies were instrumental in uncovering a direct correlation between deregulated PI3K/PTEN signaling and changes in neuronal morphogenesis, which is likely to have profound bearings upon the pathogenesis of neurological symptoms. This review outlines recent work on the function of PTEN during vertebrate brain development and the current understanding of the signaling pathways downstream of PTEN that control neuronal connectivity in the brain.

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“…It has been revealed that PTEN plays a key function for DNA repair and viability following DNA-damaging UVB radiation [ 16 ]. In addition, previous report showed that PTEN knockout mice lead to hypertrophic optic nerve [ 17 ]. Furthermore, recent studies have reported that inactivation of PTEN significantly disrupts intercellular adhesion in the RPE, which leads to AMD-like retinal degeneration in mice [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

Long

Huang

et al. 2017

BioMed Research International

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Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin-α (one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.

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Optic Nerve Alterations in PTEN^+/–Mice

Abstract: The morphologic and morphometric results suggest that heterozygous PTEN knockout mice had hypertrophic ON without ultrastructural alterations.

Cited by 3 publications

References 19 publications

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

Function of PTEN during the Formation and Maintenance of Neuronal Circuits in the Brain

PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

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Optic Nerve Alterations in PTEN+/–Mice

Abstract: The morphologic and morphometric results suggest that heterozygous PTEN knockout mice had hypertrophic ON without ultrastructural alterations.

Cited by 3 publications

References 19 publications

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

The QKI-6 and QKI-7 RNA Binding Proteins Block Proliferation and Promote Schwann Cell Myelination

Function of PTEN during the Formation and Maintenance of Neuronal Circuits in the Brain

PTEN Reduced UVB-Mediated Apoptosis in Retinal Pigment Epithelium Cells

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Optic Nerve Alterations in PTEN^+/–Mice