Photoreceptor degeneration in two mouse models for congenital stationary night blindness type 2

Regus-Leidig H, Atorf J, Feigenspan A, Kremers J, Maw MA, Brandstätter JH (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Book Volume: 9

Pages Range: e86769

Journal Issue: 1

DOI: 10.1371/journal.pone.0086769

Abstract

Light-dependent conductance changes of voltage-gated Cav1.4 channels regulate neurotransmitter release at photoreceptor ribbon synapses. Mutations in the human CACNA1F gene encoding the ?1F subunit of Cav1.4 channels cause an incomplete form of X-linked congenital stationary night blindness (CSNB2). Many CACNA1F mutations are loss-of-function mutations resulting in non-functional Cav1.4 channels, but some mutations alter the channels' gating properties and, presumably, disturb Ca(2+) influx at photoreceptor ribbon synapses. Notably, a CACNA1F mutation (I745T) was identified in a family with an uncommonly severe CSNB2-like phenotype, and, when expressed in a heterologous system, the mutation was shown to shift the voltage-dependence of channel activation, representing a gain-of-function. To gain insight into the pathomechanism that could explain the severity of this disorder, we generated a mouse model with the corresponding mutation in the murine Cacna1f gene (I756T) and compared it with a mouse model carrying a loss-of-function mutation (?Ex14-17) in a longitudinal study up to eight months of age. In ?Ex14-17 mutants, the b-wave in the electroretinogram was absent, photoreceptor ribbon synapses were abnormal, and Ca(2+) responses to depolarization of photoreceptor terminals were undetectable. In contrast, I756T mutants had a reduced scotopic b-wave, some intact rod ribbon synapses, and a strong, though abnormal, Ca(2+) response to depolarization. Both mutants showed a progressive photoreceptor loss, but degeneration was more severe and significantly enhanced in the I756T mutants compared to the ?Ex14-17 mutants.

Authors with CRIS profile

Involved external institutions

University of Otago New Zealand (NZ)

How to cite

APA:

Regus-Leidig, H., Atorf, J., Feigenspan, A., Kremers, J., Maw, M.A., & Brandstätter, J.H. (2014). Photoreceptor degeneration in two mouse models for congenital stationary night blindness type 2. PLoS ONE, 9(1), e86769. https://doi.org/10.1371/journal.pone.0086769

MLA:

Regus-Leidig, Hanna, et al. "Photoreceptor degeneration in two mouse models for congenital stationary night blindness type 2." PLoS ONE 9.1 (2014): e86769.

BibTeX: Download