title: Hematologic characterization and chromosomal localization of the novel dominantly inherited mouse hemolytic anemia, neonatal anemia (Nan).
abstract: One of the most commonly inherited anemias in man is Hereditary Spherocytosis (HS) with an incidence of 1 in 2000 for persons of Northern European descent. Mouse models of HS include spontaneous inherited hemolytic anemias and those generated by gene targeting. The Neonatal anemia (Nan) mouse is a novel model of HS generated by N-ethyl-N-nitrosurea mutagenesis and suffers from a severe neonatal anemia. Adult Nan mice have a lifelong hemolytic anemia with decreased red blood cell numbers, hematocrit, and hemoglobin, but elevated zinc protoporphyrin levels. Blood smears taken from Nan mice show a hypochromic anemia characterized by poikilocytosis, anisocytosis and polychromasia. The Nan phenotype can be transferred by bone marrow transplantation indicating that the defect is intrinsic to bone marrow. The hemolytic anemia in adult Nan mice can be identified by osmotic fragility testing. Examination of the erythrocyte membrane skeleton proteins (EMS) reveals a global deficiency of these proteins with protein 4.1a being completely absent. The Nan locus maps to mouse Chromosome 8 and does not co-localize with any known EMS genes. The identification of the Nan gene will likely uncover a novel protein that contributes to the stability of the EMS and may identify a new mutation for HS.
authors.affiliation: Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, MO 64108, USA. rwhite@cmh.edu
authors.forename: Robert A
authors.initials: RA
authors.lastname: White
authors.forename: Inna V
authors.initials: IV
authors.lastname: Sokolovsky
authors.forename: Margaret I
authors.initials: MI
authors.lastname: Britt
authors.forename: Ndona N
authors.initials: NN
authors.lastname: Nsumu
authors.forename: Derek P
authors.initials: DP
authors.lastname: Logsdon
authors.forename: Steven G
authors.initials: SG
authors.lastname: McNulty
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Wilmes
authors.forename: Brandon P
authors.initials: BP
authors.lastname: Brewer
authors.forename: Eric
authors.initials: E
authors.lastname: Wirtz
authors.forename: Heather R
authors.initials: HR
authors.lastname: Joyce
authors.forename: Barbara
authors.initials: B
authors.lastname: Fegley
authors.forename: Ann
authors.initials: A
authors.lastname: Smith
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Heruth
mesh_terms: D000743:Anemia, Hemolytic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016026:Bone Marrow Transplantation; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000378:metabolism* / Q000473:pathology; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning
chemical_list: D008565:Membrane Proteins