Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity

The rod-derived cone viability factors, RdCVF and RdCVF2, have potential therapeutical interests for the treatment of inherited photoreceptor degenerations. In the mouse lacking Nxnl2, the gene encoding RdCVF2, the progressive decline of the visual performance of the cones in parallel with their deg...

Full description

Saved in:
Bibliographic Details
Published in:Human molecular genetics 2012-05, Vol.21 (10), p.2298-2311
Main Authors: JAILLARD, Céline, MOURET, Aurélie, RAFFELSBERGER, Wolfgang, KINZEL, Bernd, TREMBLEAU, Alain, POCH, Olivier, BENNETT, Jean, WOLFRUM, Uwe, LLEDO, Pierre-Marie, SAHEL, José-Alain, LEVEILLARD, Thierry, NIEPON, Marie-Laure, CLERIN, Emmanuelle, YING YANG, LEE-RIVERA, Irene, AÏT-ALI, Najate, MILLET-PUEL, Géraldine, CRONIN, Therese, SEDMAK, Tina
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Survival - genetics
Cells, Cultured
Eye Proteins - genetics
Eye Proteins - metabolism
Fundamental and applied biological sciences. Psychology
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Life Sciences
Mice
Molecular and cellular biology
Retinal Rod Photoreceptor Cells - metabolism
RNA Splicing
Sensory Receptor Cells - cytology
Sensory Receptor Cells - metabolism
Thioredoxins - genetics
Thioredoxins - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The rod-derived cone viability factors, RdCVF and RdCVF2, have potential therapeutical interests for the treatment of inherited photoreceptor degenerations. In the mouse lacking Nxnl2, the gene encoding RdCVF2, the progressive decline of the visual performance of the cones in parallel with their degeneration, arises due to the loss of trophic support from RdCVF2. In contrary, the progressive loss of rod visual function of the Nxnl2-/- mouse results from a decrease in outer segment length, mediated by a cell autonomous mechanism involving the putative thioredoxin protein RdCVF2L, the second spliced product of the Nxnl2 gene. This novel signaling mechanism extends to olfaction as shown by the progressive impairment of olfaction in aged Nxnl2-/- mice and the protection of olfactory neurons by RdCVF2. This study shows that Nxnl2 is a bi-functional gene involved in the maintenance of both the function and the viability of sensory neurons.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/dds050