Figure 4.

A Recessive c.1000G>A (p.Ala334Thr) Mutation in KIF3B Is a Likely Cause for Progressive Retinal Atrophy in Bengal Cats

(A) Manhattan plot of GWAS for cat progressive retinal atrophy. After Bonferroni correction, several SNPs on cat chromosome A3 suggest a significant association with Bengal cat progressive retinal atrophy (Table S5). Cat chromosome A3 has genes homologous to human chromosome 20.

(B) Morphological and cellular changes as analyzed by immunohistochemistry. Left panel, anti-Kif3b antibody labels the region of the photoreceptor inner segment (IS) in wild-type cats. Similar labeling was detectable in sections from 8-week-old KIF3B homozygous mutants, but not in sections from 20-week-old mutant kittens. See Table S3 for details of antibodies used. Central panel, combination staining of the cone markers peanut agglutinin (PNA; cone sheath) with cone ML opsin (MLO). Cone morphology in KIF3B mutants at 8 weeks appears relatively normal but by 20 weeks there was distortion and stunting of outer segments with reduced ML opsin labeling. By 34 weeks of age, only short residual PNA labeling material remained with reduced ML opsin labeling. The outer nuclear layer (ONL) was progressively thinned. Right panel, labeling with a rhodopsin marker (RetP1). Rhodopsin is mislocalized in mutants to the inner segment as early as 8 weeks of age, then mislocalized to the outer nuclear layer cells bodies and synaptic terminals by 20 weeks. The rod inner and outer segments (OS) also showed some degeneration with disease progression.