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Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice
J A Shavit1, H Motohashi, K Onodera
1Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500 USA.
Abstract:
The small Maf proteins (MafG, MafK, and MafF), which serve as heterodimeric partner molecules of CNC family proteins for binding in vitro to MARE sites, have been implicated in the regulation of both transcription and chromatin structure, but there is no current evidence that the proteins fulfill these functions in vivo. To elucidate possible contributions of the small Maf proteins to gene regulation, we have ablated the mafG and mafK genes in mice by replacing their entire coding sequences with the Escherichia coli lacZ gene. mafG homozygous mutant animals exhibit impaired platelet formation accompanied by megakaryocyte proliferation, as well as behavioral abnormalities, whereas mafK-null mutant mice are phenotypically normal. Characterization of the mafG and mafK embryonic expression patterns show that their developmental programs are distinct and intersecting, but not entirely overlapping. These results provide direct evidence that the small Maf transcription factors are vital participants in embryonic development and cellular differentiation.
Insights
Small Maf proteins (MafG, MafK) are crucial for embryonic development and cellular differentiation. Ablating mafG in mice caused developmental defects, while mafK ablation had no observable effects.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- Small Maf proteins (MafG, MafK, MafF) partner with CNC proteins to bind MARE sites.
- These proteins are implicated in transcription and chromatin regulation, but in vivo evidence is lacking.
Purpose of the Study:
- To investigate the in vivo roles of small Maf proteins in gene regulation.
- To elucidate the contribution of MafG and MafK to embryonic development and cellular differentiation.
Main Methods:
- Gene ablation of mafG and mafK in mice using Escherichia coli lacZ gene replacement.
- Phenotypic characterization of homozygous mafG and mafK mutant animals.
- Analysis of mafG and mafK embryonic expression patterns.
Main Results:
- MafG homozygous mutants displayed impaired platelet formation, megakaryocyte proliferation, and behavioral abnormalities.
- MafK-null mutant mice were phenotypically normal.
- Distinct and partially overlapping embryonic expression patterns were observed for mafG and mafK.
Conclusions:
- Provides direct evidence for the vital role of small Maf transcription factors in embryonic development.
- Demonstrates the essential function of MafG in cellular differentiation and development.
- Highlights the distinct roles of MafG and MafK in developmental processes.