Congenital Stationary Night Blindness in Mice – A Tale of Two Cacna1f Mutants

Lodha, Nidhi; Bonfield, Stephan; Orton, Noelle C.; Doering, Clinton J.; McRory, John E.; Mema, Silvina C.; Rehak, Renata; Sauvé, Yves; Tobias, Rose; Stell, William K.; Bech-Hansen, N. Torben

doi:10.1007/978-1-4419-1399-9_63

Cited by 31 publications

(29 citation statements)

References 23 publications

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“…In contrast, there is ample evidence that the loss of CACNA1F gene function causes CSNB2A. For example, nonsense mutations resulting in a protein truncation already within the first third of the 1977 amino acid CACNA1F protein such as Arg50Term, Arg82Term, Glu278Term, Gln439Term, or Arg625Term associate with CSNB2A [45-47] and concordantly, Cacna1f null-mice show a CSNB2A-like phenotype [48]. The CACNA1F protein consists of four homologous domains (I-IV) and each domain is comprised of six transmembrane helices [49].…”

Section: Discussionmentioning

confidence: 99%

A Novel Large In-Frame Deletion within the CACNA1F Gene Associates with a Cone-Rod Dystrophy 3-Like Phenotype

et al. 2013

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Cone-rod dystrophies (CORDs) represent a heterogeneous group of monogenic diseases leading to early impairment of vision. The majority of CORD entities show autosomal modes of inheritance and X-linked traits are comparably rare. So far, three X-chromosomal entities were reported (CORDX1, -X2 and -X3). In this study, we analysed a large family of German origin with solely affected males over three generations showing a CORDX-like phenotype. Due to the heterogeneity of cone-rod dystrophies, we performed a combined linkage and X-exome sequencing approach and identified a novel large intragenic in-frame deletion encompassing exons 18 to 26 within the CACNA1F gene. CACNA1F is described causative for CORDX3 in a single family originating from Finland and alterations in this gene have not yet been reported in other CORDX pedigrees. Our data independently confirm CACNA1F as the causative gene for CORDX3-like phenotypes and detailed clinical characterization of the family expands the knowledge about the phenotypic spectrum of deleterious CACNA1F alterations.

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Section: Discussionmentioning

confidence: 99%

A Novel Large In-Frame Deletion within the CACNA1F Gene Associates with a Cone-Rod Dystrophy 3-Like Phenotype

et al. 2013

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“…In vision research, the OKR (sometimes called optokinetic nystagmus, or optomotor response) is used widely as a measure of visual function in studies of disease and development [7], [8], [53]–[57]. It has also been employed as an indicator of drug effects in retinal pharmacology [58]–[62].…”

Section: Discussionmentioning

confidence: 99%

Die Fledermaus: Regarding Optokinetic Contrast Sensitivity and Light-Adaptation, Chicks Are Mice with Wings

Shi

Stell

2013

PLoS ONE

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BackgroundThrough adaptation, animals can function visually under an extremely broad range of light intensities. Light adaptation starts in the retina, through shifts in photoreceptor sensitivity and kinetics plus modulation of visual processing in retinal circuits. Although considerable research has been conducted on retinal adaptation in nocturnal species with rod-dominated retinas, such as the mouse, little is known about how cone-dominated avian retinas adapt to changes in mean light intensity.Methodology/Principal FindingsWe used the optokinetic response to characterize contrast sensitivity (CS) in the chick retina as a function of spatial frequency and temporal frequency at different mean light intensities. We found that: 1) daytime, cone-driven CS was tuned to spatial frequency; 2) nighttime, presumably rod-driven CS was tuned to temporal frequency and spatial frequency; 3) daytime, presumably cone-driven CS at threshold intensity was invariant with temporal and spatial frequency; and 4) daytime photopic CS was invariant with clock time.Conclusion/SignificanceLight- and dark-adaptational changes in CS were investigated comprehensively for the first time in the cone-dominated retina of an avian, diurnal species. The chick retina, like the mouse retina, adapts by using a “day/night” or “cone/rod” switch in tuning preference during changes in lighting conditions. The chick optokinetic response is an attractive model for noninvasive, behavioral studies of adaptation in retinal circuitry in health and disease.

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“…Particular mutations in both the CACNA1F gene that encodes the ␣ 1 -subunit of an L-type Ca 2ϩ channel (Cav1.4␣) (7-10) and the CABP4 gene (11,12) were associated with this autosomal recessive retinopathy. These findings are further underscored by observations that mice lacking either CaBP4 or Cav1.4␣ display a CSNB2-like phenotype (1,13,14). The first two mutations identified in the CABP4 gene were c.800_801delAG and c.370C3 T. The first c.800_801delAG mutation causes a frameshift, p.Glu267fs, which extends the protein by 91 novel amino acids and deletes its C terminus (11).…”

Section: Cabp4mentioning

confidence: 91%

“…NMR Spectroscopy-Samples for NMR analyses were prepared by dissolving unlabeled, 15 N-labeled, 15 N, 13 C-labeled, or 2 H, 13 C, 15 N-labeled CaBP4 proteins (CaBP4(100 -271, N-lobe, and C-lobe) in 0. -bound), or 5 mM CaCl 2 (Ca 2ϩ -bound).…”

Section: Methodsmentioning

confidence: 99%

Structural Insights into Activation of the Retinal L-type Ca2+ Channel (Cav1.4) by Ca2+-binding Protein 4 (CaBP4)

Park

Haeseleer

et al. 2014

Journal of Biological Chemistry

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Background: Cav1.4 is regulated by CaBP4, which is required for continuous release of neurotransmitter in retinal photoreceptor cells. Results: CaBP4 contains two separate EF-hand lobes that bind Ca 2ϩ and form a collapsed structure around the IQ motif in Cav1.4. Conclusion: CaBP4 is suggested to activate Cav1.4 by disrupting an interaction between IQ and ICDI. Significance: CaBP4 mutations associated with congenital stationary night blindness impair its binding to IQ.

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Congenital Stationary Night Blindness in Mice – A Tale of Two Cacna1f Mutants

Cited by 31 publications

References 23 publications

A Novel Large In-Frame Deletion within the CACNA1F Gene Associates with a Cone-Rod Dystrophy 3-Like Phenotype

A Novel Large In-Frame Deletion within the CACNA1F Gene Associates with a Cone-Rod Dystrophy 3-Like Phenotype

Die Fledermaus: Regarding Optokinetic Contrast Sensitivity and Light-Adaptation, Chicks Are Mice with Wings

Structural Insights into Activation of the Retinal L-type Ca2+ Channel (Cav1.4) by Ca2+-binding Protein 4 (CaBP4)

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