The Belgrade rat has a severe microcytic, hypochromic anemia inherited as an autosomal recessive trait. Iron uptake into Belgrade reticulocytes is only about 20% of normal. The Belgrade rat carries a mutation in an unidentified protein that is involved in iron uptake through the transferrin cycle. Preliminary evidence suggests the problem may occur in endosomal acidification, with Belgrade vesicles not acidifying to the same extent as normal. If this is the case, iron uptake through the transferrin receptor and/or receptor-ligand systems other than the transferrin- transferrin receptor system may be affected. Experiments to explore this are currently underway. The results of these experiments may result in the Belgrade rat becoming an important model system for the study of endocytosis and/or endocytic acidification. The world supply of Belgrade rats, which are difficult to maintain in laboratory colonies, is in jeopardy due to a variety of circumstances. This proposal requests funds to maintain the Belgrade rat colony at the State University of New York at Buffalo.
