Marked Differences in Tissue-specific Expression of Chitinases in Mouse and Man

Two distinct chitinases have been identified in mammals: a phagocyte-specific enzyme named chitotriosidase and an acidic mammalian chitinase (AMCase) expressed in the lungs and gastrointestinal tract. Increased expression of both chitinases has been observed in different pathological conditions: chitotriosidase in lysosomal lipid storage disorders like Gaucher disease and AMCase in asthmatic lung disease. Recently, it was reported that AMCase activity is involved in the pathogenesis of asthma in an induced mouse model. Inhibition of chitinase activity was found to alleviate the inflammation-driven pathology. We studied the tissue-specific expression of both chitinases in mice and compared it to the situation in man. In both species AMCase is expressed in alveolar macrophages and in the gastrointestinal tract. In mice, chitotriosidase is expressed only in the gastrointestinal tract, the tongue, fore-stomach, and Paneth cells in the small intestine, whereas in man the enzyme is expressed exclusively by professional phagocytes. This species difference seems to be mediated by distinct promoter usage. In conclusion, the pattern of expression of chitinases in the lung differs between mouse and man. The implications for the development of anti-asthma drugs with chitinases as targets are discussed.

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Regulation of Activity and Tissue-Specific Expression of Cytochrome C Oxidase Genes under Normal and Pathological Conditions

Bioenergetics ◽

10.1007/978-1-4684-5835-0_37 ◽

1990 ◽

pp. 399-412

Author(s):

B. Kadenbach ◽

U. Büge ◽

F.-J. Hüther ◽

C. Thiel ◽

M. Droste ◽

...

Keyword(s):

Cytochrome C ◽

Cytochrome C Oxidase ◽

Specific Expression ◽

Tissue Specific ◽

Tissue Specific Expression ◽

Pathological Conditions ◽

Regulation Of Activity

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Alternative promoter usage and alternative splicing contribute to mRNA heterogeneity of mouse monocarboxylate transporter 2

Physiological Genomics ◽

10.1152/physiolgenomics.00192.2007 ◽

2007 ◽

Vol 32 (1) ◽

pp. 95-104 ◽

Cited By ~ 11

Author(s):

Shelley X. L. Zhang ◽

Tina R. Searcy ◽

Yiman Wu ◽

David Gozal ◽

Yang Wang

Keyword(s):

Transcription Factors ◽

Alternative Splicing ◽

Alternative Promoter ◽

Monocarboxylate Transporter ◽

Specific Expression ◽

Exon 2 ◽

Tissue Specific ◽

Tissue Specific Expression ◽

Exon 1 ◽

Promoter Usage

Expression patterns of monocarboxylate transporter 2 (MCT2) display mRNA diversity in a tissue-specific fashion. We cloned and characterized multiple mct2 5′-cDNA ends from the mouse and determined the structural organization of the mct2 gene. We found that transcription of this gene was initiated from five independent genomic regions that spanned >80 kb on chromosome 10, resulting in five unique exon 1 variants (exons 1a, 1b, 1c, 1d, and 1e) that were then spliced to the common exon 2. Alternative splicing of four internal exons (exons AS1, AS2, AS3, and exon 3) greatly increased the complexity of mRNA diversity. While exon 1c was relatively commonly used for transcription initiation in various tissues, other exon 1 variants were used in a tissue-specific fashion, especially exons 1b and 1d that were used exclusively for testis-specific expression. Sequence analysis of 5′-flanking regions upstream of exons 1a, 1b, and 1c revealed the presence of numerous potential binding sites for ubiquitous transcription factors in all three regions and for transcription factors implicated in testis-specific or hypoxia-induced gene expression in the 1b region. Transient transfection assays demonstrated that each of the three regions contained a functional promoter and that the in vitro, cell type-specific activities of these promoters were consistent with the tissue-specific expression pattern of the mct2 gene in vivo. These results indicate that tissue-specific expression of the mct2 gene is controlled by multiple alternative promoters and that both alternative promoter usage and alternative splicing contribute to the remarkable mRNA diversity of the gene.

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