Failure of osteoclastic bone resorption in the op rat is not due to a mutation within the coding region of the Abca3 gene.

Abstract

The spontaneous mutation in op rats produces an animal with severe osteopetrosis. This mutation has been localized to a 0.51 cM portion of RNO10. The Abca3 gene resides within this region and would be considered a functional candidate for op. In this study, we tested if this gene could be responsible for the osteopetrosis seen in the op rat. M‐13 tailed primer sets were designed from rat genomic sequence to cover the 32 exons of the rat Abca3 gene. These primer sets were amplified by PCR against genomic DNA from affected mutant animals and the two parental strains, BN and LEW. Mutational analysis of the Abca3 sequences from the three strains failed to reveal significant differences between the affected mutant animals and the two parental strains although multiple single nucleotide polymorphisms between BN and the other two strains were identified. These data indicate that the osteopetrosis seen in the op rat is not the result of a mutation within the coding region of the Abca3 gene. Analysis of additional candidate genes will be required to identify the causative mutation in this animal model of bone disease. Elucidation of the op mutation may indicate novel therapeutic paradigms in osteopetrosis, osteoporosis and rheumatoid arthritis where failed bone homeostasis is an instigating or exacerbating component of the disease process.