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Blood, Vol. 93 No. 12 (June 15), 1999:
pp. 4179-4186
Different Effect of Various Mutant MITF Encoded by mi,
Mior, or Miwh Allele on
Phenotype of Murine Mast Cells
Dae-Ki Kim,
Eiichi Morii,
Hideki Ogihara,
Young-Mi Lee,
Tomoko Jippo,
Shiro Adachi,
Kazutaka Maeyama,
Hyung-Min Kim, and
Yukihiko Kitamura
From the Department of Pathology, Osaka University Medical School,
Osaka, Japan; the Department of Pharmacology, Ehime University Medical
School, Ehime, Japan; and the Department of Oriental Pharmacy, College
of Pharmacy, Wonkwang University, Chonbuk, Republic of Korea.
The mi locus encodes a member of the
basic-helix-loop-helix-leucine zipper protein family of transcription
factors (hereafter called MITF). Mutant alleles of mi,
Mior, and Miwh are deletion or
point mutation of the basic domain by which MITF binds DNA. The basic
domain also has nuclear localization potential. In the present study,
we compared the mast cell abnormalities of
Mior/Mior and
Miwh/Miwh mice with those of
mi/mi mice, of which many have been described by us. The number
of mast cells in the skin of Mior/Mior
suckling mice was remarkably decreased from that observed in mi/mi suckling mice, but the number was normal in the skin of Miwh/Miwh suckling mice. The decrease
in skin mast cells was more severe in the mi/mi embryos than in
mi/mi suckling mice, but the magnitude of the decrease was
comparable between Mior/Mior embryos
and Mior/Mior suckling mice. The poor
mRNA expression of granzyme B and tryptophan hydroxylase genes was
observed in all cultured mast cells (CMCs) derived from the spleens of
Miwh/Miwh,
Mior/Mior, and mi/mi mice.
However, the poor expression of mouse mast cell protease-4 (MMCP-4),
MMCP-5, and MMCP-6 was observed only in
Mior/Mior and mi/mi CMCs. MITF
encoded by Miwh mutant allele
(Miwh-MITF) showed deficient but demonstratable DNA
binding, but mi-MITF and Mior-MITF did not
show any DNA binding ability. Although Miwh-MITF
and Mior-MITF showed normal nuclear localization
potential, the potential was significantly impaired in mi-MITF.
The rank order of mast cell abnormality (mi/mi > Mior/Mior > Miwh/Miwh) appears to be related to the
functional abnormality of MITF encoded by each mutant gene.
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