Homozygotes exhibit grainy retinas by 3 weeks of age which progresses into large white patches distributed across the entire retina by 12 weeks of age. At 10 days of age the apical processes of the retinal pigment epithelium are abnormally elongated, by 14 days of age the retinal outer nuclear layer is reduced in thickness and contains pyknotic nuclei and the photoreceptor outer segments are disorganized and shortened. Standard pathology work-up on two male mutants (145 or 224 days of age) revealed severe bilateral retinal degeneration.
By 3 weeks of age the photoreceptor layer is reduced to one to two layers of cells and the outer segments are not visible. Both dark and light adapted flash electroretinograms show reduced amplitude responses as early as 14 days of age and this worsens progressively to near zero by 26 days of age.
Male infertility is associated with decreased weight of the testes and epididymides and azoospermia as early as 6 weeks of age with severe degradation of spermatogenesis.
Progressive leukoencephalopathy is also found, with vacuoles in the white matter tracts and cerebellum by 7 months of age becoming more severe at 18 months of age. Despite these histological findings, accompanying behavioral abnormalities have not been found.
A C57BL/6J male was treated with N-ethyl-N-nitrosurea, bred to C57BL/6J females, an F1 male offspring was bred with a C57BL/6J female, and a female from the resulting offspring was backcrossed to its F1 grandfather to generate a population in which recessive mutations could be phenotypically identified. This mutation has been maintained on the C57BL/6J background.
|Allele Name||neuroscience mutagenesis facility, 240|
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||Clcn2, chloride channel, voltage-sensitive 2|
|Strain of Origin||C57BL/6J|
|Molecular Note||This mutation was discovered in a mutagenesis screen. A C-T nonsense mutation at base pair 1063 is predicted to result in the glutamine at amino acid 355 in the encoded protein modified to a stop codon.|