title: A Mouse Model for Human Unstable Hemoglobin Santa Ana.
abstract: In the present study, we described the phenotype, histologic morphology, and molecular etiology of a mouse model of unstable hemoglobin Santa Ana. Hematologic evaluation of anemic mice (Anem/+) discovered after N-ethyl-N-nitrosourea mutagenesis revealed moderate anemia with intense reticulocytosis and polychromasia, followed by anisocytosis, macrocytosis, hypochromia, and intraerythrocytic inclusion and Heinz bodies. The mice also demonstrated hemoglobinuria, bilirubinemia, and erythrocytic populations with differing resistance to osmotic lysis. Splenomegaly (particularly in older mutant mice) and jaundice were apparent at necropsy. Histopathologic examination revealed dramatically increased hematopoiesis and hemosiderosis in hematopoietic organs and intracellular iron deposition in tubular renal cells. These data are characteristic of a congenital hemolytic regenerative anemia, similar to human anemias due to unstable hemoglobin. Genetic mapping assigned the affected gene to mouse chromosome 7, approximately 50 cM from the Hbb locus. The sequence of the mutant Hbb gene exhibited a T→C transversion at nucleotide 179 in Hbb-b1, leading to the substitution of proline for leucine at amino acid residue 88 and thus homologous to the genetic defect underlying Santa Ana anemia in humans.
authors.affiliation: Medical Clinic Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Samantha I
authors.initials: SI
authors.lastname: Miyashiro
authors.affiliation: Department of Immunology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Silvia M G
authors.initials: SM
authors.lastname: Massironi
authors.affiliation: Department of Pathology, School of Veterinary Medicine and AnimalMedicine and Animal Science Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil;, Email: claumori@gmail.com.
authors.forename: Claudia M C
authors.initials: CM
authors.lastname: Mori
authors.affiliation: Department of Immunology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Carolina C
authors.initials: CC
authors.lastname: Cruz
authors.affiliation: Medical Clinic Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Mitika K
authors.initials: MK
authors.lastname: Hagiwara
authors.affiliation: Department of Immunology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Maiorka
mesh_terms: D000745:Anemia, Hemolytic, Congenital / Q000097:blood*; D000818:Animals; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005038:Ethylnitrosourea; D005260:Female; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000032:analysis*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation
chemical_list: D006455:Hemoglobins, Abnormal; C046185:hemoglobin Santa Ana; D005038:Ethylnitrosourea