title: Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid alpha-spectrin gene.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Jackson Laboratory, 600 Main St., Bar Harbor, Maine 04609, USA.
authors.forename: N J
authors.initials: NJ
authors.lastname: Wandersee
authors.forename: C S
authors.initials: CS
authors.lastname: Birkenmeier
authors.forename: E J
authors.initials: EJ
authors.lastname: Gifford
authors.forename: N
authors.initials: N
authors.lastname: Mohandas
authors.forename: J E
authors.initials: JE
authors.lastname: Barker
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D016368:Frameshift Mutation; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D013049:Spectrin / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D013103:Spherocytosis, Hereditary / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D018076:DNA, Complementary; D012333:RNA, Messenger; D013049:Spectrin