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Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice

Honjo, Yasuyuki; Nagineni, Chandrasekharam N.; Larsson, Jonas LU ; Nandula, Seshagiri R.; Hooks, John J.; Chan, Chi-Chao; Karlsson, Stefan LU and Kulkarni, Ashok B. (2007) In Biochemical and Biophysical Research Communications 352(2). p.418-422
Abstract
We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells... (More)
We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interpho to receptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE. (c) 2006 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
TGF-beta, cataracts, Cre-lox P system, chondroitin-6-sulfate, extracellular matrix, TGF-beta receptor I, retinal detachment, retinal pigment epithelium, retina
in
Biochemical and Biophysical Research Communications
volume
352
issue
2
pages
418 - 422
publisher
Elsevier
external identifiers
  • wos:000243196300022
  • scopus:33751510956
ISSN
1090-2104
DOI
10.1016/j.bbrc.2006.11.033
language
English
LU publication?
yes
id
2ff20b7f-d85b-436b-b80c-dbfcdcbf8908 (old id 680427)
date added to LUP
2007-12-12 16:04:28
date last changed
2017-01-01 06:37:25
@article{2ff20b7f-d85b-436b-b80c-dbfcdcbf8908,
  abstract     = {We generated a mouse model (cKO) with a conditional deletion of TGF-beta signaling in the retinal neurons by crossing TGF-beta receptor I (TGF-beta RI) floxed mice with nestin-Cre mice. Almost all of the newborn cKO mice had retinal detachment at the retinal pigment epithelium (RPE)/photoreceptor layer junction of the neurosensory retina (NSR). The immunostaining for chondroitin-6-sulfate showed a very weak reaction in cKO mice in contrast to intense staining in the photoreceptor layer in wild-type mice. Macroscopic cataracts, in one or both eyes, were observed in 50% of the mice by 6 months of age, starting as early as the first month after birth. The cKO mouse model demonstrates that the TGF-beta signaling deficiency in retinal cells leads to decreased levels of chondroitin sulfate proteoglycan in the retinal interpho to receptor matrix. This in turn causes retinal detachment due to the loss of adhesion of the NSR to RPE. (c) 2006 Elsevier Inc. All rights reserved.},
  author       = {Honjo, Yasuyuki and Nagineni, Chandrasekharam N. and Larsson, Jonas and Nandula, Seshagiri R. and Hooks, John J. and Chan, Chi-Chao and Karlsson, Stefan and Kulkarni, Ashok B.},
  issn         = {1090-2104},
  keyword      = {TGF-beta,cataracts,Cre-lox P system,chondroitin-6-sulfate,extracellular matrix,TGF-beta receptor I,retinal detachment,retinal pigment epithelium,retina},
  language     = {eng},
  number       = {2},
  pages        = {418--422},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {Neuron-specific TGF-beta signaling deficiency results in retinal detachment and cataracts in mice},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2006.11.033},
  volume       = {352},
  year         = {2007},
}