This model of X-linked congenital stationary night blindness has a more severe phenotype that that of the Cacna1fnob2 mutation in AXB6/PgnJ. Degeneration of the outer plexiform layer begins by 14 days of age and progresses rapidly with ERG readings being greatly diminished by 1 month of age.Read More +
This spontaneous G to A substitution in the intron just before exon 14 created a novel CAG splice acceptor site resulting in the inclusion of 10 base pairs of intronic sequence into the 5-prime end of exon 14, which yields a frameshift and premature termination. This mutation provides a model for X-linked type 2A congenital stationary night blindness (CSNB2A). The outer plexiform layer appears to develop normally with near normal thickness at 10 days of age, but degenerates early, with diminished thickness by 14 days of age, progressing such that it is almost absent between 2 and 8 months of age. By 8 months of age small white dots are found in the fundus, mainly in the central and ventral quadrants. Homozygotes display a drastically reduced scotopic ERG. At 1 month of age the scotopic ERG shows a greatly diminished, but not absent, b-wave, which displays small oscillatory potentials. The a-wave amplitude is approximately half that of wild-type controls at 2 months of age and this degrades with age until the amplitude is approximately 27% that found in controls at 14 months of age. Photopic ERGs show drastic reduction in response, with almost no waveform by 2 months of age. At 2 months of age both S-opsins and M-opsins are present in the retinas at normal levels, but both decline with age, with the loss of M-opsins being more severe such that at 14 months of age there remain almost no M-opsins and only 54% of normal levels of S-opsins and those were found to abnormally localized to the inner photoreceptor segments. ERGs with white light, green light, and UV light failed to elicit an ERG response at 2, 8, and 14 months of age. Compared with the Cacna1fnob2 mutation characterized in the AXB6/PgnJ recombinant inbred strain, the Cacna1fnob9 mutation has a faster disease onset and more severe phenotype.
The no b-wave 9 mutation was first identified in the C57BL/6J-Chr 10.3PWD/Ph/ForeJ strain by Dr. Bo Chang at The Jackson Laboratory. A mutant male was bred to C57BL/6J and the offspring, which were all phenotypic wild-type, were intercrossed, producing 12 wild-type females, 3 wild-type males, and 4 mutant males, indicative of a recessive X-linked mutation. This mutation was then backcrossed from mutant males to C57BL/6J females until the strain reached generation N5, at which point the maintenance of the strain changed to sibling intercrossing and eventually became homozygous females bred to hemizygous males. This strain reached generation N5F21 in 2018.
|Allele Name||no b wave 9|
|Allele Type||Spontaneous (Not Specified)|
|Gene Symbol and Name||Cacna1f, calcium channel, voltage-dependent, alpha 1F subunit|
|Strain of Origin||C57BL/6J-Chr 10.3PWD/Ph/ForeJ|
|Molecular Note||This spontaneous mutation involves an intronic G-to-A substitution, which creates a novel CAG splice acceptor site. Use of this ectopic acceptor creates a mis-spliced transcript with a 10 bp 5' extension of exon 14 that results in a frameshift and premature stop codon.|