Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis. Blood 2001 Jan 15;97(2):543-50
Date
01/12/2001Pubmed ID
11154235DOI
10.1182/blood.v97.2.543Scopus ID
2-s2.0-0035863842 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
Mutations affecting the conversion of spectrin dimers to tetramers result in hereditary elliptocytosis (HE), whereas a deficiency of human erythroid alpha- or beta-spectrin results in hereditary spherocytosis (HS). All spontaneous mutant mice with cytoskeletal deficiencies of spectrin reported to date have HS. Here, the first spontaneous mouse mutant, sph(Dem)/ sph(Dem), with severe HE is described. The sph(Dem) mutation is the insertion of an intracisternal A particle element in intron 10 of the erythroid alpha-spectrin gene. This causes exon skipping, the in-frame deletion of 46 amino acids from repeat 5 of alpha-spectrin and alters spectrin dimer/tetramer stability and osmotic fragility. The disease is more severe in sph(Dem)/sph(Dem) neonates than in alpha-spectrin-deficient mice with HS. Thrombosis and infarction are not, as in the HS mice, limited to adults but occur soon after birth. Genetic background differences that exist between HE and HS mice are suspect, along with red blood cell morphology differences, as modifiers of thrombosis timing. sph(Dem)/sph(Dem) mice provide a unique model for analyzing spectrin dimer- to-tetramer conversion and identifying factors that influence thrombosis.
Author List
Wandersee NJ, Roesch AN, Hamblen NR, de Moes J, van der Valk MA, Bronson RT, Gimm JA, Mohandas N, Demant P, Barker JEMESH terms used to index this publication - Major topics in bold
Age FactorsAnimals
Animals, Newborn
Base Sequence
Dimerization
Disease Models, Animal
Electrophoresis, Polyacrylamide Gel
Elliptocytosis, Hereditary
Erythrocytes
Gene Deletion
Genes, Intracisternal A-Particle
Hematologic Tests
Introns
Mice
Mice, Mutant Strains
Molecular Sequence Data
Mutation
Spectrin
Thrombosis
Tissue Distribution