Behavioral Phenotypic Properties of a Natural Occurring Rat Model of Congenital Stationary Night Blindness With Cacna1f Mutation

Abstract

Cacna1f gene mutation could lead to incomplete congenital stationary night blindness (iCSNB) disease. The CSNB-like phenotype rat is a spontaneous rat model caused by Cacna1f gene mutation. The present study explored the phenotypic properties of behavior performance in CSNB rats further. The vision-related behaviors of CSNB rats were assessed with a Morris water maze (MWM), passive avoidance tests, and open-field test. Motor ability was evaluated with a rotarod test and a wire hang test, and mechanical pain and thermalgia were used to evaluate sensory system function. Electroretinograms (ERGs) were recorded to evaluate the function of the retina. The vision-related results showed that longer latencies of escape and reduced probe trial in MWM for CSNB rats. There were more errors in avoidance test; CSNB rats were more active in the open field and presented a different pattern of exploration. The locomotor-related behaviors showed shorter falling latencies in the rotarod test and shorter gripping time in CSNB rats. And mechanical thresholds of pain increased in CSNB rats. The ERGs indicated that both the amplitude and latency of rod and cone systems were impaired in the CSNB rats. In summary, Cacna1f gene mutation changed the performance of various behaviors in the CSNB rat aside from vision-related phenotype. Cacna1f gene might play a role in a wide range of responses in the organism. These results confirm the importance of a comprehensive profile for understanding the behavior phenotype of Cacna1f gene mutation in CSNB rat.

Spectrum of Cav1.4 dysfunction in congenital stationary night blindness type 2

“…12, I745T was indistinguishable from wild type Cav1.4 (n = 4 − 6). This protocol was designed to mimic conditions of light illumination (at the holding potential) with short periods of darkness (during the test pulse); 5 Hz is a low frequency used to assess the flicker fusion frequency under conditions for scotopic rod vision [31]. We therefore conclude that, under physiological conditions, truncation of the C-terminus of Cav1.4 results in a loss-of-function because the truncated channels are incapable of supporting continuous calcium influx during changes in illumination.…”

Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia

“…The closely-related Ca v 3.1 has been shown to be a key element in the pathophysiology of a mouse model of trigeminal neuropathic pain ( Choi et al., 2016 ). Mechanical thresholds of pain are significantly altered in a rat model of congenital stationary night blindness with a Cacna1f mutation ( An et al., 2012 ). Detailed electrophysiology of these TN-associated SCN5A , CACNA1H , and CACNA1F channel variants in cell culture systems and animal models will be rich topics for future investigation.…”

Light‐responsive microRNA miR‐211 targets Ezrin to modulate lysosomal biogenesis and retinal cell clearance

“…Photopic cone responses were isolated in light conditions with a constant background illumination of 50 cd/m 2 , with 10 flashes and a light intensity of 20 cd s/m 2 . Cone response was then better isolated using Flicker analysis (An et al , ). Mice were stimulated with a fixed frequency of 6 Hz and flashes of 13 different light intensities, ranging from 10 −4 to 15 cd s/m 2 generated by the Ganzfeld stimulator.…”