THE HYPOTRANSFERRINAEMIC MOUSE - ULTRASTRUCTURAL AND LASER MICROPROBEANALYSIS OBSERVATIONS

Homozygote hypotransferrinaemic mice (hpx/hpx) have cytopathological f eatures similar to those of human congenital atransferrinaemia, geneti c haemochromatosis, and neonatal haemochromatosis. These conditions al l have in common high levels of cytotoxic non-transferrin-bound serum iron. This study describes the ultrastructural features of iron overlo ad in liver, pancreas, heart, and small intestine of 2- and 12-month-o ld hypotransferrinaemic mice. Electron microscopic studies of unstaine d sections showed early parenchymal cell siderosis, with accumulation of numerous ferritin particles and clusters in the cytosol, as well as ferritin and haemosiderin in lysosomes (siderosomes). In the 12-month -old animals, iron was also found in Kupffer cells and macrophages in other tissues. In addition, there were conspicuous iron-containing com pounds in the bile canaliculi; and marked iron deposition in the pancr eas and heart. Laser microprobe mass analysis (LAMMA) enabled localiza tion and relative quantitation of iron deposition in subcellular compa rtments providing in situ documentation of iron accumulation in sidero somes and contributed in assessing total cytosolic iron in various cel l types. Moreover, it demonstrated the importance and magnitude of the biliary route for iron excretion in these animals.