Submitted September 7, 2007
Accepted March 19, 2008
hem6: an ENU-induced recessive hypochromic microcytic anemia mutation in the mouse
Meng Tian, Dean R Campagna, Lanette S Woodward, Monica J Justice, and Mark D Fleming*
Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA, United States
Department of Genetics, Baylor College of Medicine, Houston, TX, United States
* Corresponding author; email: mark.fleming{at}childrens.harvard.edu.
Mouse models have proven invaluable for understanding erythropoiesis. Here, we describe an autosomal recessive, inherited anemia in the mouse mutant hem6. Hematologic and transplantation analyses reveal a mild, congenital, hypochromic, microcytic anemia intrinsic to the hematopoietic system that is associated with a decreased red blood cell zinc protoporphyrin to heme ratio, indicative of porphyrin insufficiency. Intercross matings show that hem6 can suppress the porphyric phenotype of mice with erythropoietic protoporphyria (EPP). Furthermore, iron uptake studies in hem6 reticulocytes demonstrate defective incorporation of iron into heme that can be partially corrected by the addition of porphyrin precursors. Gene expression and enzymatic assays indicate that erythroid 5-aminolevulinic acid synthase (Alas2) is decreased in hem6 animals, suggesting a mechanism that could account for the anemia. Overall, these data lead to the hypothesis that hem6 encodes a protein that directly or indirectly regulates the expression of Alas2.
