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Characterisation of electrogenic nutrient absorption in the Cftr TgH(neoim)Hgu mouse model

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Abstract

Most cystic fibrosis (CF) patients show an exocrine pancreatic insufficiency that results in lower enzyme and bicarbonate secretion. To test whether an altered function of nutrient transporters might additionally attribute to the lower bodyweight of CF patients we investigated electrogenic absorption of alanine, glycyl-glutamine, glucose and the effect of pH on nutrient absorption by Ussing chambers in a CF mouse model carrying the Cftr TgH(neoim)Hgu mutation. The electrogenic transport of all three nutrients was similar between the D2.129P2(CF/3)-Cftr TgH(neoim)Hgu congenic strain and DBA/2J mice as well as between the B6.129P2(CF/3)-Cftr TgH(neoim)Hgu congenic strain and C57BL/6J mice. This indicates that the Cftr TgH(neoim)Hgu mutation does not affect the electrogenic absorption of alanine, glycyl-glutamine and glucose. In contrast, electrogenic nutrient absorption was reduced in the CF/1-Cftr TgH(neoim)Hgu and CF/3-Cftr TgH(neoim)Hgu inbred strains compared to the HsdOla:MF1, D2.129P2(CF/3)-Cftr TgH(neoim)Hgu and B6.129P2(CF/3)-Cftr TgH(neoim)Hgu strains, whereas no difference was found among the wild-type strains. This indicates that not the Cftr TgH(neoim)Hgu mutation but differences in the genetic background of the CF/1-Cftr TgH(neoim)Hgu and CF/3-Cftr TgH(neoim)Hgu strains compared to HsdOla:MF1, D2.129P2(CF/3)-Cftr TgH(neoim)Hgu and B6.129P2(CF/3)-Cftr TgH(neoim)Hgu strains are associated with the differences in electrogenic nutrient absorption. The electrogenic absorption of alanine, glycyl-glutamine and glucose was not influenced by an acidic pH (5.4) compared to absorption at pH 7.4.

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Abbreviations

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator (human)

Cftr:

Cystic fibrosis transmembrane conductance regulator (murine)

NHE3:

Na+/H+ Exchanger isoform 3

PEPT1:

Peptide transporter isoform 1

WT:

Wild-type

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (Research Training Group 705). The authors gratefully acknowledge for the animal care to Petra Adomat and Harry Detterming as well as for the excellent technical assistance of M. Burmester, M. Loh and U. Dringenberg in the Ussing chamber experiments. All experiments were approved by the local government as well as by the local Institutional Animal Care and Research Advisory Committee.

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Authors and Affiliations

  1. Department of Physiology, University of Veterinary Medicine Hannover, Bischofsholer Damm 15/102, 30173, Hannover, Germany

    B. Tóth, S. Leonhard-Marek & G. Breves

  2. Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    H. J. Hedrich

Authors
  1. B. Tóth
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  2. S. Leonhard-Marek
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  3. H. J. Hedrich
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  4. G. Breves
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Corresponding author

Correspondence to G. Breves.

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Communicated by G. Heldmaier.

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Tóth, B., Leonhard-Marek, S., Hedrich, H.J. et al. Characterisation of electrogenic nutrient absorption in the Cftr TgH(neoim)Hgu mouse model. J Comp Physiol B 178, 705–712 (2008). https://doi.org/10.1007/s00360-008-0259-7

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  • DOI: https://doi.org/10.1007/s00360-008-0259-7

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