Transporters for di- and tripeptides are found in prokaryotes and eukaryotes. In mammals two different transport systems have been identified. PEPT1 (SLC15A1) is mainly expressed in the small intestine and mediates the absorption of dietary di- and tripeptides from protein breakdown in the gut. PEPT2 (SLC15A2) shows a widespread expression within the mammalian organism. In kidney it mainly mediates the reabsorption of filtered di- and tripeptides, but its role in other tissues such as lung, mammary gland or brain has not yet been determined.

In Caenorhabditis elegans a homologue to mammalian PEPT1 is encoded by the pep-2 gene and we have generated a line of animals lacking pep-2 expression to study the role of this transporter in protein metabolism. We localised the expression of the PEPT1-homologue in C. elegans in intestinal cells and sensoric neurons in the head by using a GFP-transgene construct. To study the physiological role of the PEP2 transporter in vivo, we generated a C. elegans pep-2 deletion mutant. The animals deficient in pep-2 show a remarkable phenotype with pronounced signs of malnutrition. The development from larval to adult stage is severely retarded and the generation-time is extended 2-fold compared with wild-type animals. Moreover, they carry less eggs in the uterus, have a severely reduced brood size but possess a prolonged mean lifespan compared with wild-type (wt) animals. It was possible to rescue the phenotype by the expression of the wt pep-2 gene in the mutant. The C. elegans mutant eat-2, described as feeding defective, exhibits a very similar phenotype that is caused by caloric restriction. The observed starved phenotype in pep-2 mutants might therefore be best explained by the reduced intestinal absorption of peptide bound amino acids that are required for protein synthesis and energy metabolism and providing the first direct evidence for the predominant role of the intestinal peptide in amino acid absorption. As pep-2 is also expressed in neuronal cells of the nematode, experiments are in progress to identify these neurons. Since the physiological role of a proton-coupled peptide transporter in neurons is currently unknown, C. elegans may provide a useful model system to study this function in vivo.

To determine the physiological role of the PEPT2 protein, we isolated the Pept2 gene from mice (Rubio-Aliaga et al. 2000) that made it possible to construct a targeting vector for the generation of a Pept2 knock-out mice strain. The targeting vector included the bacterial β-galactosidase gene under the control of the Pept2-promoter in the Pept2^-/- mice allowing us to study the expression of the Pept2-gene at the cellular level. We shall present first information on the Lac-Z expression in Pept2^-/- mice and discuss the possible physiological function of the PEPT2 protein in the tissues and cells identified.