These Spta1sph-Dem mice exhibit severe hereditary elliptocytosis (HE). 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 homozygous neonates than in alpha-spectrin-deficient mice with hereditary spherocytosis (HS). Thrombosis and infarction are not limited to adults but occur soon after birth. These mice provide a unique model for analyzing spectrin dimer- to-tetramer conversion and identifying factors that influence thrombosis.
|Gene Symbol and Name||Spta1, spectrin alpha, erythrocytic 1|
|Strain of Origin||CcS3/Dem|
|Molecular Note||Sequence analysis of genomic DNA shows this allele is the result of an intracisternal A particle transposon insertion into intron 10 of the erythroid alpha-spectrin gene. This leads to abnormal splicing and an in-frame deletion of 46 amino acids from repeat 5 of alpha spectrin.|