Life Sciences Division
Oak Ridge National Laboratory

The Role of the Gene, fitness 1 (fit1), in iron metabolism and anemia (May 1998)

The two common disturbances of iron balance in humans are iron deficiency and iron overload, both of which may lead to anemia. Scientists in the Mammalian Genetics and Development Section of the Life Sciences Division are analyzing a mouse gene, fitness 1 (fit1), that provides a useful model for the study of the genetic control of the regulation of iron metabolism in man and mammals. The researchers have five mouse stocks, each carrying a different mutation experimentally induced in the fit1 gene, that are anemic, apparently due to their inability to reutilize an overload of iron stored in their livers. The five mutant stocks exhibit different severities of anemia, depending on the DNA site of the induced mutation; in its most severe form, the mutation is lethal to mice before the age of weaning. Even in the least severe of the series of fit1 mutations, the affected mice are runted and ill, and have abnormal red blood cells. One of the mutations in fit1 also causes a severe scoliosis in affected pups.

The fit1 gene lies within the complex of radiation-induced chromosomal deletions that surround the mouse albino locus. Using genetic crosses, the group has localized the interval that contains the fit1 gene to a DNA segment no larger than 360 kb. They have constructed a map of DNA clones that spans this interval, and will search the clones by DNA sequencing for candidate genes. Collaborator Dr. Eric Schultze, veterinary clinical hematologist at The University of Tennessee College of Veterinary Medicine, is analyzing the alterations in growth, in blood cell formation, and in serum chemistry profiles in the fit1 mutants. He is also performing measurements of physiological indicators of iron metabolism and iron distributions in the five mutant lines. Pinpointing the site of mutation in each of the abnormal fit1 genes will allow us to correlate the functional deficit with the accompanying structural alteration caused by the mutation. (Contact: D. K. Johnson, 574-0953 or k29@ornl.gov)