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Molecular and Cellular Biology, May 2003, p. 3247-3252, Vol. 23, No. 9
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.9.3247-3252.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Targeted Disruption of the Peptide Transporter Pept2 Gene in Mice Defines Its Physiological Role in the Kidney

Isabel Rubio-Aliaga,1 Isabelle Frey,1 Michael Boll,1 David A. Groneberg,2 Hans M. Eichinger,3 Rudi Balling,4,{dagger} and Hannelore Daniel1*

Molecular Nutrition Unit, Technical University of Munich, D-85350 Freising-Weihenstephan,1 Department of Pediatric Pneumology and Immunology, Charite Campus Virchow, Humboldt University, D-13353 Berlin,2 HVA, Technical University of Munich, 85350 Freising,3 GSF-National Research Center for Environment and Health, Institute of Mammalian Genetics, D-85764 Neuherberg, Germany4

Received 2 December 2002/ Returned for modification 21 January 2003/ Accepted 10 February 2003

The peptide transporter PEPT2 mediates the cellular uptake of di- and tripeptides and selected drugs by proton-substrate cotransport across the plasma membrane. PEPT2 was functionally identified initially in the apical membrane of renal tubular cells but was later shown to be expressed in other tissues also. To investigate the physiological importance of PEPT2 and for a detailed analysis of the protein expression sites, we generated a Pept2 knockout mouse line in which the Pept2 gene was disrupted by insertion of a ß-galactosidase gene under the control of the PEPT2 promoter. The Pept2-/- mice showed no obvious phenotypic abnormalities but also no adaptive upregulation in the expression level of related genes in the kidney. The importance of PEPT2 in the reabsorption of filtered dipeptides was demonstrated in knockout animals by significantly reduced renal accumulation of a fluorophore-labeled and a radiolabeled dipeptide after in vivo administration of the tracers. This indicates that PEPT2 is the main system responsible for tubular reabsorption of peptide-bound amino acids, although this does not lead to major changes in renal excretion of protein or free amino acids.

* Corresponding author. Mailing address: Molecular Nutrition Unit, Technical University of Munich, Hochfeldweg 2, D-85350 Freising-Weihenstephan, Germany. Phone: 49 8161 713400. Fax: 49 8161 713999. E-mail: daniel{at}wzw.tum.de.

{dagger} Present address: German Research Centre for Biotechnology, D-38124 Braunschweig, Germany.

Molecular and Cellular Biology, May 2003, p. 3247-3252, Vol. 23, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.9.3247-3252.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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