Faculty Research 1990 - 1999

Title

Ankyrin and the hemolytic anemia mutation, nb, map to mouse chromosome 8: presence of the nb allele is associated with a truncated erythrocyte ankyrin.

Document Type

Article

Publication Date

1990

Keywords

Anemia-Hemolytic: ge, Animal, Blood-Proteins: ge, Chromosome-Mapping, Chromosomes-Human-Pair-8, Crosses-Genetic, Erythrocyte-Membrane: an, Erythrocytes: me, Female, Human, Isoenzymes: ge, Linkage-(Genetics), Male, Membrane-Proteins: ge, Mice, Mice-Inbred-C57BL, Mice-Inbred-Strains, Mutation, Reticulocytes: an, SUPPORT-U-S-GOVT-P-H-S

JAX Location

Reprint Collection : 1789

JAX Source

Proc Natl Acad Sci USA 1990 Apr; 87(8):3117-21.

Grant

HL29305

Abstract

Mice with normoblastosis, nb/nb, have a severe hemolytic anemia. The extreme fragility and shortened lifespan of the mutant erythrocytes result from a defective membrane skeleton. Previous studies in our laboratory indicated a 50% deficiency of spectrin and an absence of normal ankyrin in erythrocyte membranes of nb/nb mice. We now report genetic mapping data that localize both the nb and erythroid ankyrin (Ank-1) loci to the centromeric end of mouse chromosome 8. Using immunological and biochemical methods, we have further characterized the nature of the ankyrin defect in mutant erythrocytes. We do not detect normal sized (210 kDa) erythroid ankyrin by immunoblot analysis in nb/nb reticulocytes. However, nb/nb reticulocytes do contain a 150-kDa ankyrin immunoreactive protein. The 150-kDa protein is present with normal-sized ankyrin in nb/+ reticulocytes but is not found in +/+ reticulocytes. Our genetic and biochemical data indicate that the nb mutation results from a defect in the erythroid ankyrin gene. A human hereditary spherocytosis putatively resulting from an ankyrin defect maps to a segment of human chromosome 8 that is homologous to the nb-ankyrin region of mouse chromosome 8. The linkage data suggest that the mouse and human diseases result from mutations in homologous loci.