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Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-07-2213.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1344-1350
HEMATOPOIESIS
Additive effect of mouse genetic background and mutation of
MITF gene on decrease of skin mast cells
Eiichi Morii,
Keisuke Oboki,
Tomoko Jippo, and
Yukihiko Kitamura
From the Department of Pathology, Medical
School/Graduate School of Frontier Bioscience, Osaka University,
Yamada-oka, Suita, Japan.
The mi transcription factor (MITF) is a
basic-helix-loop-helix leucine zipper transcription factor and is
encoded by mi locus. The mi/mi mutant mice
showed a significant decrease of skin mast cells in C57BL/6 (B6)
genetic background but not in WB genetic background. Kit ligand (KitL)
is the most important growth factor for development of mast cells, and
the decrease of skin mast cells in B6-mi/mi mice was
attributable to the reduced expression of c-kit receptor
tyrosine kinase (KIT) that is a receptor for KitL. However, the
expression level of KIT in WB-mi/mi mast cells was comparable with that of B6-mi/mi mast cells, suggesting
that a factor compensating the reduced expression of KIT was present in
WB-mi/mi mice. By linkage analysis, such a factor was
mapped on chromosome 10. The mapped position was closely located to the KitL locus. Two alternative spliced forms are known in KitL mRNA: KL-1
and KL-2. Soluble KitL, which is important for development of skin mast
cells, is produced more efficiently from KL-1 mRNA than from KL-2 mRNA.
The KL-1/KL-2 ratio was higher in WB-mi/mi than in
B6-mi/mi mice, suggesting that the larger amount of soluble KitL may compensate for the reduced expression of KIT in
WB-mi/mi mice.

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