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Blood, 1 April 2001, Vol. 97, No. 7, pp. 2038-2044
HEMATOPOIESIS
Importance of leucine zipper domain of mi
transcription factor (MITF) for differentiation of mast cells
demonstrated using mice/mice mutant
mice of which MITF lacks the zipper domain
Eiichi Morii,
Hideki Ogihara,
Dae-Ki Kim,
Akihiko Ito,
Keisuke Oboki,
Young-Mi Lee,
Tomoko Jippo,
Shintaro Nomura,
Kazutaka Maeyama,
M. Lynn Lamoreux, and
Yukihiko Kitamura
From the Department of Pathology, Osaka University
Medical School, Suita, Japan; Department of Oriental Pharmacy, Wonkwang
University, Iksan, Korea; Department of Pharmacology, Ehime University
Medical School, Ehime, Japan; and the Department of Veterinary
Pathobiology, Texas A&M University, College Station, TX.
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 mice mutant
allele (ce-MITF) lacks the Zip domain. We examined the importance of the Zip domain using
mice/mice mice. The amounts of
c-kit, granzyme B (Gr B), and tryptophan hydroxylase (TPH)
messenger RNAs decreased in mast cells of
mice/mice 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
mice/mice 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 mice/mice 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.
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