Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.

The Rgcs1 quantitative trait locus, on mouse chromosome 5, influences susceptibility of retinal ganglion cells to acute damage of the optic nerve. Normally resistant mice (DBA/2J) congenic for the susceptible allele from BALB/cByJ mice exhibit susceptibility to ganglion cells, not only in acute opti...

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Main Authors: Joel A Dietz, Margaret E Maes, Shuang Huang, Brian S Yandell, Cassandra L Schlamp, Angela D Montgomery, R Rand Allingham, Michael A Hauser, Robert W Nickells
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093564&type=printable
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author Joel A Dietz
Margaret E Maes
Shuang Huang
Brian S Yandell
Cassandra L Schlamp
Angela D Montgomery
R Rand Allingham
Michael A Hauser
Robert W Nickells
author_facet Joel A Dietz
Margaret E Maes
Shuang Huang
Brian S Yandell
Cassandra L Schlamp
Angela D Montgomery
R Rand Allingham
Michael A Hauser
Robert W Nickells
author_sort Joel A Dietz
collection DOAJ
description The Rgcs1 quantitative trait locus, on mouse chromosome 5, influences susceptibility of retinal ganglion cells to acute damage of the optic nerve. Normally resistant mice (DBA/2J) congenic for the susceptible allele from BALB/cByJ mice exhibit susceptibility to ganglion cells, not only in acute optic nerve crush, but also to chronic inherited glaucoma that is characteristic of the DBA/2J strain as they age. SNP mapping of this QTL has narrowed the region of interest to 1 Mb. In this region, a single gene (Spink2) is the most likely candidate for this effect. Spink2 is expressed in retinal ganglion cells and is increased after optic nerve damage. This gene is also polymorphic between resistant and susceptible strains, containing a single conserved amino acid change (threonine to serine) and a 220 bp deletion in intron 1 that may quantitatively alter endogenous expression levels between strains. Overexpression of the different variants of Spink2 in D407 tissue culture cells also increases their susceptibility to the apoptosis-inducing agent staurosporine in a manner consistent with the differential susceptibility between the DBA/2J and BALB/cByJ strains.
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publishDate 2014-01-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-9f5b02ad14dc4ceba5cfe49d6a15feba2025-08-20T02:14:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9356410.1371/journal.pone.0093564Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.Joel A DietzMargaret E MaesShuang HuangBrian S YandellCassandra L SchlampAngela D MontgomeryR Rand AllinghamMichael A HauserRobert W NickellsThe Rgcs1 quantitative trait locus, on mouse chromosome 5, influences susceptibility of retinal ganglion cells to acute damage of the optic nerve. Normally resistant mice (DBA/2J) congenic for the susceptible allele from BALB/cByJ mice exhibit susceptibility to ganglion cells, not only in acute optic nerve crush, but also to chronic inherited glaucoma that is characteristic of the DBA/2J strain as they age. SNP mapping of this QTL has narrowed the region of interest to 1 Mb. In this region, a single gene (Spink2) is the most likely candidate for this effect. Spink2 is expressed in retinal ganglion cells and is increased after optic nerve damage. This gene is also polymorphic between resistant and susceptible strains, containing a single conserved amino acid change (threonine to serine) and a 220 bp deletion in intron 1 that may quantitatively alter endogenous expression levels between strains. Overexpression of the different variants of Spink2 in D407 tissue culture cells also increases their susceptibility to the apoptosis-inducing agent staurosporine in a manner consistent with the differential susceptibility between the DBA/2J and BALB/cByJ strains.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093564&type=printable
spellingShingle Joel A Dietz
Margaret E Maes
Shuang Huang
Brian S Yandell
Cassandra L Schlamp
Angela D Montgomery
R Rand Allingham
Michael A Hauser
Robert W Nickells
Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.
PLoS ONE
title Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.
title_full Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.
title_fullStr Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.
title_full_unstemmed Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.
title_short Spink2 modulates apoptotic susceptibility and is a candidate gene in the Rgcs1 QTL that affects retinal ganglion cell death after optic nerve damage.
title_sort spink2 modulates apoptotic susceptibility and is a candidate gene in the rgcs1 qtl that affects retinal ganglion cell death after optic nerve damage
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093564&type=printable
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