On the C57BL/6J congenic background, in the absence of the Pde6brd1 allele, homozygotes for the retinal pigment epithelium atrophy 1 mutation (Prkcqrpea1) have a blotchy and spotted fundus appearance beginning at 6 weeks of age. At 16 days of age there is an aberrant staining pattern of the filamentous actin ring structure in the retinal pigment epithelium. Optical coherence tomography imaging at 30 days of age detected areas of shallow retinal detachments. Although the outer segments are intact at 30 days, their apical ends appear disorganized. Electron microscopy showed that the apical microvilli of the retinal pigment epithelium abuts the abnormal outer segment tips instead of extending between them. By 6 weeks of age retinal detachment is found in a pattern that correlates with the reduced pigmentation found by ophthalmoscopy, and the detachments increase in number and dimension with age. At 60 days of age, but not 30 days of age, choroidal blood vessels in the areas of retinal detachment are larger than normal with thickened walls. Fluorescein leakage from retinal blood vessels was not found at 2 or 6 months of age. Photoreceptor cell degeneration occurs and at 45 weeks of age is found both in areas of retinal detachment and normal attachment. At 45 weeks of age there are focal areas of retinal pigment epithelium atrophy, with pigmented and nonpigmented nucleated cells found in the subretinal space. A decrease in adhesion strength between the retinal pigment epithelium and the photoreceptor outer segments was indicated by a reduction in the retinal pigment epithelial pigment attached to the neural retina when peeled from the eyecup. The matrix sheath around the cone outer segment is redistributed into the outer nuclear layer at 60 days of age, but not 30 days of age. Electroretinograms show only a slight decline in response at 1 month of age, but at 6 months of age homozygotes have a reduced rod response and only slightly reduced cone response. Mice doubly homozygous for Prkcqrpea1 and Prd6brd1 (see stock #018777) have a more severe phenotype with star-shaped fundus pattern and complete retinal detachment by 1 month of age, and by 6 months of age enlarged eyes, high intraocular pressure, cataracts, and ganglion and photoreceptor cell loss.
The retinal pigment epithelium atrophy 1 mutation (Prkcqrpea1) arose spontaneously in the strain ABJ/LeJ and was backcrossed onto the C57BL/6J background. The Pde6brd1 allele from ABJ/LeJ was bred out of this congenic strain. After generation N5 this strain was fixed to homozygosity for Prkcqrpea1. In 2017 this strain reached generation N5F17.
|Allele Name||retinal pigment epithelium atrophy 1|
|Allele Type||Spontaneous (Null/Knockout)|
|Gene Symbol and Name||Prkcq, protein kinase C, theta|
|Strain of Origin||ABJ/LeJ|
|Molecular Note||A G-to-A transition in the fifth base in intron 6 (GTAAG to GTAAA) affects the splice donor site causes skipping of exon 6, a frameshift, and premature stop codon. Protein was not detected by western blot analysis on extracts of eye, indicating that this is a null allele.|