title: Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity.
abstract: 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.
authors.affiliation: Institut de la vision, INSERM, U968, Paris F-75012, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Jaillard
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mouret
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Niepon
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Clérin
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Irene
authors.initials: I
authors.lastname: Lee-Rivera
authors.forename: Najate
authors.initials: N
authors.lastname: Aït-Ali
authors.forename: Géraldine
authors.initials: G
authors.lastname: Millet-Puel
authors.forename: Thérèse
authors.initials: T
authors.lastname: Cronin
authors.forename: Tina
authors.initials: T
authors.lastname: Sedmak
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Raffelsberger
authors.forename: Bernd
authors.initials: B
authors.lastname: Kinzel
authors.forename: Alain
authors.initials: A
authors.lastname: Trembleau
authors.forename: Olivier
authors.initials: O
authors.lastname: Poch
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Lledo
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.forename: Thierry
authors.initials: T
authors.lastname: Léveillard
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D012326:RNA Splicing; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism
chemical_list: D005136:Eye Proteins; C525118:RdCVF-2 protein, mouse; D013879:Thioredoxins