Date Submitted


Faculty Advisor

Robert White, Ph.D.

Second Faculty Advisor

Gregory Fitch, Ph.D.

Third Faculty Advisor

Marshall Andersen, Ph.D.


Adult Hereditary Hemochromatosis (HH) is a disease that causes uncontrollable iron absorption. This results in excess iron in vital organs which leads to numerous pathologies including diabetes, liver cirrhosis and cardiomyopathy. The current treatments for HH are the use of iron chelating drugs and phlebotomy. Alternatively, Juvenile Hemochromatosis (JH) occurs in children and is particularly much worse than adult hemochromatosis due to the fact it happens much earlier in life and develops at a much faster rate. The only treatment available for patients with JH is phlebotomy and compliance is a challenge due to the painful nature of this type of treatment. As an alternative, a novel treatment of Juvenile Hemochromatosis may be uncovered by studying an iron deficiency anemia mouse mutant called flaky skin (fsn). The name of this autosomal recessive mutant mouse derives from the psoriasis-like condition which accompanies their iron deficiency anemia. The fsn homozygous mice excrete 100 times more iron in the urine than normal mice because of a mutated protein called TTC7 (Tetratricopeptide repeat domain 7). This protein is found in the kidneys and we hypothesize that the production of an abnormal protein (TTC7: Tetratricopeptide repeat domain 7) causes substantial urinary iron excretion, thus leading to the iron deficiency anemia. Our hypothesis is that the presence of this mutation in the heterozygous state in hemochromatosis model mice could prevent iron overload and therefore uncover a novel treatment of hemochromatosis including JH. The results presented in this work indicate that JH mice, that are carrying the fsn mutation from the mouse mutant excreting high amount of iron in urine, do not show any impact on iron overloading. However, in a previous study of 10-week-old Hereditary 2 Hemochromatosis model mice carrying the fsn mutation, iron overload is prevented. There is also the finding that there is only a delay in iron overloading in these mice since, at 15 weeks, of age these mice become iron overloaded. The strategy for future experiments is to determine how the delay occurs in these mice and to ascertain how to make the prevention of iron overload into a more permanent condition.