Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid alpha-spectrin gene. Hematol J 2000;1(4):235-42
Date
03/29/2002Pubmed ID
11920196DOI
10.1038/sj.thj.6200030Scopus ID
2-s2.0-0034584411 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
INTRODUCTION: Spectrin, a heterodimer of alpha- and beta-subunits, is the major protein component of the red blood cell membrane skeleton. The mouse mutation, sph, causes an alpha-spectrin-deficient hereditary spherocytosis with the severe phenotype typical of recessive hereditary spherocytosis in humans. The sph mutation maps to the erythroid alpha-spectrin locus, Spna1, on Chromosome 1.
MATERIALS AND METHODS: Scanning electron microscopy, osmotic gradient ektacytometry, cDNA cloning, RT-PCR, nucleic acid sequencing, and Northern blot analyses were used to characterize the wild type and sph alleles of the Spna1 locus.
RESULTS: Our results confirm the spherocytic nature of sph/sph red blood cells and document a mild spherocytic transition in the +/sph heterozygotes. Sequencing of the full length coding region of the Spna1 wild type allele from the C57BL/6J strain of mice reveals a 2414 residue deduced amino acid sequence that shows the typical 106-amino-acid repeat structure previously described for other members of the spectrin protein family. Sequence analysis of RT-PCR clones from sph/sph alpha-spectrin mRNA identified a single base deletion in repeat 5 that would cause a frame shift and premature termination of the protein. This deletion was confirmed in sph/sph genomic DNA. Northern blot analyses of the distribution of Spna1 mRNA in non-erythroid tissues detects the expression of 8, 2.5 and 2.0 kb transcripts in adult heart.
CONCLUSION: These results predict the heart as an additional site where alpha-spectrin mutations may produce a phenotype and raise the possibility that a novel functional class of small alpha-spectrin isoforms may exist.
Author List
Wandersee NJ, Birkenmeier CS, Gifford EJ, Mohandas N, Barker JEMESH terms used to index this publication - Major topics in bold
AllelesAmino Acid Sequence
Animals
Base Sequence
DNA, Complementary
Frameshift Mutation
Genotype
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Molecular Sequence Data
Myocardium
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Sequence Deletion
Spectrin
Spherocytosis, Hereditary
Structure-Activity Relationship
