title: hem6: an ENU-induced recessive hypochromic microcytic anemia mutation in the mouse.
abstract: 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.
authors.affiliation: Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Tian
authors.forename: Dean R
authors.initials: DR
authors.lastname: Campagna
authors.forename: Lanette S
authors.initials: LS
authors.lastname: Woodward
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Justice
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis* / Q000235:genetics; D000747:Anemia, Hypochromic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D006410:Hematopoiesis / Q000235:genetics; D006418:Heme / Q000096:biosynthesis / Q000235:genetics; D007501:Iron / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D046351:Protoporphyria, Erythropoietic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012156:Reticulocytes / Q000201:enzymology* / Q000473:pathology
chemical_list: D006418:Heme; D007501:Iron; D000624:5-Aminolevulinate Synthetase
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