Importance of leucine zipper domain of mi transcription factor (MITF) for differentiation of mast cells demonstrated using mi(ce)/mi(ce) mutant mice of which MITF lacks the zipper domain.
The mi transcription factor (MITF) is a basic helix-loop-helix leucine zipper (bHLH-Zip) transcription factor that is important for the development of mast cells. Mast cells of mi/mi genotype express normal amount of abnormal MITF (mi-MITF), whereas mast cells of tg/tg genotype do not express any MITFs. Mast cells of mi/mi mice show more severe abnormalities than those of tg/tg mice, indicating that the mi-MITF possesses the inhibitory function. The MITF encoded by the mi(ce) mutant allele (ce-MITF) lacks the Zip domain. We examined the importance of the Zip domain using mi(ce)/mi(ce) mice. The amounts of c-kit, granzyme B (Gr B), and tryptophan hydroxylase (TPH) messenger RNAs decreased in mast cells of mi(ce)/mi(ce) mice to levels comparable to those of tg/tg mice, and the amounts were intermediate between those of +/+ mice and those of mi/mi mice. Gr B mediates the cytotoxic activity of mast cells, and TPH is a rate-limiting enzyme for the synthesis of serotonin. The cytotoxic activity and serotonin content of mi(ce)/mi(ce) mast cells were comparable to those of tg/tg mast cells and were significantly higher than those of mi/mi mast cells. The phenotype of mi(ce)/mi(ce) mast cells was similar to that of tg/tg mast cells rather than to that of mi/mi mast cells, suggesting that the ce-MITF had no functions. The Zip domain of MITF appeared to be important for the development of mast cells. (Blood. 2001;97:2038-2044)
Morii
E
E
Department of Pathology, Osaka University Medical School, Suita, Japan. morii@patho.med.osaka-u.ac.jp
Ogihara
H
H
Kim
D K
DK
Ito
A
A
Oboki
K
K
Lee
Y M
YM
Jippo
T
T
Nomura
S
S
Maeyama
K
K
Lamoreux
M L
ML
Kitamura
Y
Y
D000818:Animals; D002268:Carboxypeptidases / Q000096:biosynthesis / Q000235:genetics; D043422:Carboxypeptidases A; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D004790:Enzyme Induction; D005260:Female; D053804:Granzymes; D016350:Leucine Zippers / Q000235:genetics / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051739:Microphthalmia-Associated Transcription Factor; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D012701:Serotonin / Q000096:biosynthesis; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection; D053802:Tryptases; D014365:Tryptophan Hydroxylase / Q000235:genetics
D004268:DNA-Binding Proteins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D012333:RNA, Messenger; C509190:Tpsb2 protein, mouse; D014157:Transcription Factors; D012701:Serotonin; D004247:DNA; D014365:Tryptophan Hydroxylase; D019009:Proto-Oncogene Proteins c-kit; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D053804:Granzymes; C509214:Gzmb protein, mouse; D012697:Serine Endopeptidases; C066932:mast cell protease 4; C509222:Tpsab1 protein, mouse; D053802:Tryptases