Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice

Ko Onodera, Jordan A. Shavit, Hozumi Motohashi, Masayuki Yamamoto, James Douglas Engel

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

Prior studies exploring the mechanisms controlling erythroid gene regulation implicated MARE (Maf recognition element) cis-elements as crucial to the transcriptional activity of many erythroid genes. Numerous transcription factors can elicit responses through MAREs, including not only the AP-1 family proteins, but also a growing list of factors composed of Cap-N-Collar (CNC)-small Maf heterodimers. While these factors can activate transcription from MAREs in co-transfection assays, mouse germline mutations in cnc genes tested to date have failed to reveal primary erythroid phenotypes. Here we report that after combining the mafK and mafG targeted null alleles, mutant animals display several synthetic phenotypes, including erythroid deficiencies. First, compound homozygous small maf gene mutants survive embryogenesis, but die postnatally. Secondly, compound mutant animals develop severe neurological disorders. Thirdly, they exhibit an exacerbated mafG deficiency in megakaryopoiesis, specifically in proplatelet formation, resulting in profound thrombocytopenia. Finally, the compound mutant animals develop severe anemia accompanied by abnormal erythrocyte morphology and membrane protein composition. These data provide direct evidence that the small Maf transcription factors play an important regulatory role in erythropoiesis.

Original languageEnglish
Pages (from-to)1335-1345
Number of pages11
JournalEMBO Journal
Volume19
Issue number6
DOIs
Publication statusPublished - 2000 Mar 15
Externally publishedYes

Keywords

  • Anemia
  • Cytoskeleton
  • Platelet
  • Small Maf
  • Spherocytosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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