RGD Reference Report - Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis. - Rat Genome Database

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Defective spectrin integrity and neonatal thrombosis in the first mouse model for severe hereditary elliptocytosis.

Authors: Wandersee, NJ  Roesch, AN  Hamblen, NR  De Moes, J  Van der Valk, MA  Bronson, RT  Gimm, JA  Mohandas, N  Demant, P  Barker, JE 
Citation: Wandersee NJ, etal., Blood. 2001 Jan 15;97(2):543-50.
RGD ID: 11059523
Pubmed: PMID:11154235   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hereditary elliptocytosis  ISOSpta1 (Mus musculus)11059523; 11059523DNA:insertion:intron:RGD 
hereditary elliptocytosis  IAGP 11059523DNA:insertion:intron:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Spta1  (spectrin, alpha, erythrocytic 1)

Genes (Mus musculus)
Spta1  (spectrin alpha, erythrocytic 1)

Genes (Homo sapiens)
SPTA1  (spectrin alpha, erythrocytic 1)


Additional Information