Journal
EMBO JOURNAL
Volume 19, Issue 6, Pages 1335-1345Publisher
OXFORD UNIV PRESS
DOI: 10.1093/emboj/19.6.1335
Keywords
anemia; cytoskeleton; platelet; small Maf; spherocytosis
Categories
Funding
- NCI NIH HHS [R01 CA080088, R01 CA80088, P30 CA060553, P30 CA60553] Funding Source: Medline
- NIGMS NIH HHS [T32 GM08152, T32 GM008152] Funding Source: Medline
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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.
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