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.

• MeSH
• Aneuploidy MeSH
• Bone Marrow Cells cytology   MeSH
• Factor VIII genetics   metabolism   MeSH
• Femur cytology   metabolism   ultrastructure   MeSH
• Animals, Genetically Modified MeSH
• Histological Techniques MeSH
• Bone and Bones metabolism   ultrastructure   MeSH
• Rabbits MeSH
• Humans MeSH
• RNA, Messenger metabolism   MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• F8 protein, human MeSH Browser
• Factor VIII MeSH
• RNA, Messenger MeSH

Differences in microscopic structure of the femur between 1-month-old transgenic rabbits carrying the hFVIII gene and non-transgenic rabbits were investigated. Bone microstructure was evaluated from the point of view of qualitative and quantitative histological characteristics. We identified fibrolamellar bone tissue only in the transgenic animals. Measured values for area, perimeter of the Haversian canals and minimum diameter of the primary osteons' vascular canals were higher in 1-month-old transgenic individuals (P < 0.05; P < 0.001). We also observed lower concentrations of Ca, P, K, solids, and total mineral content in femora of transgenic rabbits. A statistically significant difference was observed for the concentration of Ca (P < 0.05). Our results indicate evident changes in both qualitative and quantitative histological characteristics of the femur, which result especially in better blood supply and slightly reduced mineralization process in 1-month-old transgenic rabbits.

• MeSH
• Factor VIII genetics   MeSH
• Femur cytology   MeSH
• Calcification, Physiologic MeSH
• Animals, Genetically Modified MeSH
• Bone Density MeSH
• Rabbits MeSH
• Humans MeSH
• Milk Proteins genetics   MeSH
• Animals, Newborn MeSH
• Animals MeSH
• Check Tag
• Rabbits MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Factor VIII MeSH
• Milk Proteins MeSH
• whey acidic proteins MeSH Browser