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Gene expression profiling in the submandibular gland, stomach, and duodenum of CAVI-deficient mice

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An Erratum to this article was published on 16 February 2011

Abstract

Carbonic anhydrase VI (CAVI) is the only secreted isozyme of the α-carbonic anhydrase family, which catalyzes the reversible reaction \( {\text{CO}}_{2} + {\text{H}}_{2} {\text{O}} \Leftrightarrow {\text{HCO}}_{3}^{ - } + {\text{H}}^{ + } \). It appears that CAVI protects teeth and gastrointestinal mucosa by neutralizing excess acidity. However, the evidence for this physiological function is limited, and CAVI may have additional functions that have yet to be discovered. To explore the functions of CAVI more fully, we generated Car6 −/− mice and analyzed Car6 −/− mutant phenotypes. We also examined transcriptomic responses to CAVI deficiency in the submandibular gland, stomach, and duodenum of Car6 −/− mice. Car6 −/− mice were viable and fertile and had a normal life span. Histological analyses indicated a greater number of lymphoid follicles in the small intestinal Peyer’s patches. A total of 94, 56, and 127 genes were up- or down-regulated in the submandibular gland, stomach, and duodenum of Car6 −/− mice, respectively. The functional clustering of differentially expressed genes revealed a number of altered biological processes. In the duodenum, the significantly affected biological pathways included the immune system process and retinol metabolic processes. The response to oxidative stress and brown fat cell differentiation changed remarkably in the submandibular gland. Notably, the submandibular gland, stomach, and duodenum shared one important transcriptional susceptibility pathway: catabolic process. Real-time PCR confirmed an altered expression in 14 of the 16 selected genes. The generation and of Car6 −/− mice and examination of the effects of CAVI deficiency on gene transcription have revealed several affected clusters of biological processes, which implicate CAVI in catabolic processes and the immune system response.

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Abbreviations

ATP:

Adenosine triphosphate

CA:

Carbonic anhydrase

ERG:

Electroretinogram

ES:

Embryo stem

GO:

Gene ontology

PAGE:

Polyacrylamide gel electrophoresis

PBS:

Phosphate-buffered saline

qRT–PCR:

Quantitative real-time polymerase chain reaction

RT-PCR:

Reverse transcription-polymerase chain reaction

SDS:

Sodium dodecyl sulfate

TK:

Thymidine kinase

VLAD:

Visual annotation display

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Acknowledgments

The authors thank Zahid Shah, PhD, for valuable help in the construction of the targeting vector, and Alejandra Rodriguez Martinez, PhD, Marja Paloniemi, and the Biocenter Oulu Transgenic Core Facility for the technical assistance. This work was supported by grants from the Academy of Finland, the EU Framework 6 program (DeZnIT), and the Medical Fund of the Tampere University Hospital (9L071).

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Authors and Affiliations

  1. Institute of Medical Technology, University of Tampere, Biokatu 6, 33520, Tampere, Finland

    Pei-wen Pan & Seppo Parkkila

  2. School of Medicine, University of Tampere, Tampere, Finland

    Seppo Parkkila

  3. Centre for Laboratory Medicine, Tampere University Hospital, University of Tampere, Tampere, Finland

    Pei-wen Pan & Seppo Parkkila

  4. Department of Anatomy and Cell Biology, Institute of Biomedicine, University of Oulu, Oulu, Finland

    Katri Käyrä, Jukka Leinonen, Marja Nissinen & Hannu Rajaniemi

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  1. Pei-wen Pan
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  2. Katri Käyrä
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  3. Jukka Leinonen
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  4. Marja Nissinen
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  5. Seppo Parkkila
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  6. Hannu Rajaniemi
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Correspondence to Pei-wen Pan.

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The authors Pei-wen Pan and Katri Käyrä contributed equally to this work.

An erratum to this article can be found at http://dx.doi.org/10.1007/s11248-011-9487-9

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Pan, Pw., Käyrä, K., Leinonen, J. et al. Gene expression profiling in the submandibular gland, stomach, and duodenum of CAVI-deficient mice. Transgenic Res 20, 675–698 (2011). https://doi.org/10.1007/s11248-010-9441-2

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