Changes of femoral bone tissue microstructure in transgenic rabbits.

Bone tissue microstructure of femur was investigated in transgenic New Zealand White rabbits with human factor VIII gene. Altogether 42 bones (24 from transgenic rabbits and 18 from non-transgenic ones) were analysed. Specimens were prepared using standard histological equipment, producing thin sections of approximately 80-100 microm. For histomorphometrical analysis areas, perimeters, minimum and maximum diameters of osteons' vascular canals and of osteons were measured. We found out that the basic structural pattern of femoral bone tissue was primary vascular longitudinal in both groups of rabbits. However, a new type of the bone tissue--fibrolamellar--was identified only in the transgenic rabbits. The measured variables of the osteons' vascular canals were higher in transgenic individuals in comparison with the nontransgenic ones (except for maximal diameter) and the differences were statistically significant (P < 0.05; P < 0.01). We suppose that the observed differences could be associated with transgenesis. In an effort to explain these differences we compared the cytogenetic profile of bone marrow cells between transgenic and non-transgenic rabbits. A significantly higher rate of aneuploidy was observed in c-metaphase spreads of transgenic individuals as compared to non-transgenic ones (P < 0.001). Despite the fact that no hFVIII mRNA expression was found in the femur of transgenic rabbits, we discussed an association of transgene integration into the genome and microstructural changes in the bone. In any case, the results indicate that transgenesis can also produce changes in other tissues than in the target ones.