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Independent influence of strain difference and mi transcription factor on the expression of mouse mast cell chymases.

ABSTRACT: Expression of mouse mast cell protease (mMCP) genes was examined with particular attention to the transactivation effect of mi transcription factor (MITF) and the expression differences between C57BL/6 (B6) and WB strains. We had reported the enhancing effect of MITF on the expression of mMCP-4, -5, and -6 genes in cultured mast cells (CMCs) of B6 strain, and in the present study we demonstrated the enhancing effect on the expression of mMCP-2 and -9 genes as well. The enhancing effect of MITF on the expression of mMCP-2, -4, -5, -6, and -9 genes was also detected in CMCs of the WB strain. The regulation of mMCP-2, -4, and -9 genes was localized to a specific promoter element (CANNTG) which was recognized and bound by MITF and which was conserved between the B6 and WB strains. On the other hand, the expression of mMCP-2, -4, and -9 genes was smaller in CMCs of the B6 strain when compared to their expression in CMCs of the WB strain. Although mMCP-5 is a chymase as mMCP-2, -4, and -9, and genes encoding all of the chymases are located on chromosome 14, the mMCP-5 gene was regulated in a manner distinct from mMCP-2, -4, and -9 genes.

SUBMITTER: Ge Y

PROVIDER: S-EPMC1850270 | biostudies-literature | 2001 Jan

REPOSITORIES: biostudies-literature

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Independent influence of strain difference and mi transcription factor on the expression of mouse mast cell chymases.

Ge Y Y Jippo T T Lee Y M YM Adachi S S Kitamura Y Y

The American journal of pathology 20010101 1

Expression of mouse mast cell protease (mMCP) genes was examined with particular attention to the transactivation effect of mi transcription factor (MITF) and the expression differences between C57BL/6 (B6) and WB strains. We had reported the enhancing effect of MITF on the expression of mMCP-4, -5, and -6 genes in cultured mast cells (CMCs) of B6 strain, and in the present study we demonstrated the enhancing effect on the expression of mMCP-2 and -9 genes as well. The enhancing effect of MITF o ...[more]

PMID: 11141502

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Project description:Microphthalmia-associated transcription factor (Mitf) is expressed in neural crest cell-derived melanocytes, and in the retinal pigment epithelium (RPE) during ocular development. Mutations in Mitf are associated with auditory/visual/pigmentary syndromes in humans. Mitf(mi/mi) mouse mutants lack pigmentation, and are microphthalmic, while Mitf(vit/vit) mouse mutants display abnormal RPE pigmentation, and progressive retinal degeneration. Microarray analysis was used to identify novel downstream gene targets/pathways in the RPE that are altered by mutations in the transcription factor Mitf. Using the Affymetrix platform, gene expression profiles were generated using the eyes of E13.5 mouse fetuses that were wildtype, heterozygous, or homozygous for the Mitf(mi) mutation. In a separate experiment, eyes from E13.5 mouse fetuses homozygous for the Mitf(vit) mutation were compared to eyes from the C57BL/6 control background strain. Statistical analyses were performed using robust multiarray average, mixed-effects ANOVA and random-variance t-tests. Altered expression of genes involved in pigment formation, melanosome biogenesis/transport, and redox homeostasis were observed. Twelve genes were commonly mis-regulated in the eyes of both Mitf mutants: 10 of these genes were downregulated in both mutants relative to controls, while 2 of the genes (Nramp1 (Slc11a1) and epoxide hydrolase) were downregulated in Mitf(mi/mi) mutants, and conversely, upregulated in Mitf(vit/vit) mutants. Quantitative RT-PCR and immunohistochemistry were used to confirm altered gene/protein expression. RPE expression of the Fe(+2) iron transporter Nramp1 (Slc11a1) has not previously been reported. Fe(+2) is an important co-factor utilized by the iron-dependent isomerohydrolase RPE65 in the retinoid visual cycle. However, excess accumulation of Fe(+2) in the RPE has recently been associated with oxidative damage and age-related macular degeneration. Abnormal pigmentation and increased activity of Slc11a1 in the RPE of Mitf(vit) mice may contribute to the pathology and progressive retinal degeneration observed in these mutants.

Dataset Information

Independent influence of strain difference and mi transcription factor on the expression of mouse mast cell chymases.

Publications

Independent influence of strain difference and mi transcription factor on the expression of mouse mast cell chymases.

Similar Datasets

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