Dominant interfering alleles define a role for c-Myb in T-cell development.
The transcription activator c-Myb is expressed at high levels in immature thymocytes and during T-cell activation and may be a regulator of T-cell differentiation. To investigate the role of c-Myb in T-cell development, we generated transgenic mice in which two dominant interfering Myb alleles, one a competitive inhibitor of DNA binding, and the other, an active repressor comprising the Myb DNA-binding domain linked to the Drosophila Engrailed transcription repressor domain, were expressed from early times onward in T cells. Both alleles partially blocked thymopoiesis and inhibited proliferation of mature T cells. The Myb-En chimera was the more efficient repressor and might serve as an archetype for the manufacture of other dominant interfering transcription factor alleles.
Badiani
P
P
Institute of Cancer Research, Chester Beatty Laboratories, London, UK.
Corbella
P
P
Kioussis
D
D
Marvel
J
J
Weston
K
K
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005799:Genes, Dominant / Q000502:physiology; D018398:Homeodomain Proteins; D007301:Insect Hormones / Q000235:genetics; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins; D017384:Sequence Deletion / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C063459:En protein, Drosophila; D018398:Homeodomain Proteins; D007301:Insect Hormones; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors