Model mice for Presbyterian hemoglobinopathy (Asnβ108→Lys) confer hemolytic anemia with altered oxygen affinity and instability of Hb

Yo ichi Suzuki, Takahiko Shimizu, Hiromi Sakai, Masakatsu Tamaki, Ken ichi Koizumi, Takayuki Kuriyama, Eishun Tsuchida, Haruhiko Koseki, Takuji Shirasawa

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Hb Presbyterian is a variant hemoglobin that carries Lys at Asn-108 of β-globin. This variant Lysβ108 residue enhances the stability of Hb in the deoxy-state, conferring the low affinity for oxygen-binding in vitro. In the present study, we generated mutant mice carrying the Presbyterian mutation (Asnβ108 → Lys) at the β-globin locus by a targeted knock-in strategy. Heterozygous mice showed the expression of Hb Presbyterian in 27.7% of total peripheral blood without any hematological abnormalities, which well mimicked human cases. On the other hand, homozygous mice exclusively expressed Hb Presbyterian in 100% of peripheral blood associated with hemolytic anemia, Heinz body formation, and splenomegaly. Hb Presbyterian showed instability in an in vitro precipitation assay. Erythrocytes from homozygous mice showed a shortened life span when transfused into wild-type mice, confirming that the knocked-in mutation of Lysβ108 caused hemolysis in homozygous mice. This is the first report on the hemolytic anemia of unstable hemoglobin in an animal model. These results confirm the notion that the higher ratio of an unstable variant β-globin chain in erythrocytes triggers the pathological precipitation and induces hemolysis in abnormal hemoglobinopathies.

Original languageEnglish
Pages (from-to)869-876
Number of pages8
JournalBiochemical and biophysical research communications
Volume295
Issue number4
DOIs
Publication statusPublished - 2002 Sep 28

Keywords

  • Hemoglobin
  • Hemolytic anemia
  • Knock-in mice
  • Low oxygen affinity
  • Presbyterian
  • Unstable Hb

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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