Evaluation of the APOH gene as a positional candidate for prcd in dogs.

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Abstract

PURPOSE: Progressive rod-cone degeneration (prcd) is an autosomal recessive retinal degeneration of dogs characterized by abnormalities in lipid metabolism. It has recently been mapped to the centromeric region of canine chromosome 9, homologous to human 17q, which contains the apolipoprotein H (apoH, protein; APOH, gene) gene involved in lipid metabolism and regulation of triglycerides. The present study was undertaken to evaluate APOH as a positional candidate for prcd. METHODS: Expression of APOH in the retina was examined by reverse transcription-polymerase chain reaction (RT-PCR) and by immunocytochemistry in normal and prcd-affected dogs. The level of apoH in the plasma was determined by western blot analysis. Intragenic polymorphic markers were identified and typed in the prcd pedigree. Canine-rodent hybrid cell lines were analyzed to detect canine APOH. RESULTS: ApoH has been localized to the photoreceptor outer segment layer by immunocytochemistry. Its expression in the retina of normal and prcd-affected dogs was confirmed by RT-PCR. The levels of antihuman apoH cross-reacting material in plasma were similar in all dogs, regardless of disease status. Finally, linkage analysis of the APOH gene with the disease locus in the prcd pedigree detected 3 recombinants among 70 informative offsprings (lod score 15.09 at 0 = 4.3 centimorgan [cM]). CONCLUSIONS: APOH is expressed in the retina and tightly linked to the prcd locus. However, despite its potential role in phenotypes of abnormal lipid metabolism associated with prcd, the gene has been excluded as a primary candidate for prcd by linkage analysis.