Singer D Camargo SM Ramadan T Schäfer M Mariotta L Herzog B Huggel K Wolfer D Werner S Penninger JM Verrey F 2012 Mutations in the main intestinal and kidney luminal neutral amino acid transporter B(0)AT1 (Slc6a19) lead to Hartnup disorder, a condition that is characterized by neutral aminoaciduria and in some cases pellagra-like symptoms. These latter symptoms caused by low-niacin are thought to result from defective intestinal absorption of its precursor L-tryptophan. Since Ace2 is necessary for intestinal B(0)AT1 expression, we tested the impact of intestinal B(0)AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na(+)-dependent uptake of B(0)AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na(+)-dependent transport of L-proline, presumably via SIT1 (Slc6a20), was absent, whereas glucose uptake via SGLT1 (Slc5a1) was not affected. Measurements of small intestine luminal amino acid content following gavage showed that more L-tryptophan than other B(0)AT1 substrates reach the ileum in wild-type mice, which is in line with its known lower apparent affinity. In ace2 null mice, the absorption defect was confirmed by a severalfold increase of L-tryptophan and of other neutral amino acids reaching the ileum lumen. Furthermore, plasma and muscle levels of glycine and L-tryptophan were significantly decreased in ace2 null mice, with other neutral amino acids displaying a similar trend. A low-protein/low-niacin diet challenge led to differential changes in plasma amino acid levels in both wild-type and ace2 null mice, but only in ace2 null mice to a stop in weight gain. Despite the combination of low-niacin with a low-protein diet, plasma niacin concentrations remained normal in ace2 null mice and no pellagra symptoms, such as photosensitive skin rash or ataxia, were observed. In summary, mice lacking Ace2-dependent intestinal amino acid transport display no total niacin deficiency nor clear pellagra symptoms, even under a low-protein and low-niacin diet, despite gross amino acid homeostasis alterations. https://sonar.ch/global/documents/235799 eng info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpgi.00140.2012 info:eu-repo/semantics/altIdentifier/pmid/22790597 American journal of physiology. Gastrointestinal and liver physiology. - 2012 Absorption Amino Acid Transport Systems, Neutral Amino Acids Animal Nutritional Physiological Phenomena Animals Diet Dietary Proteins Gene Expression Regulation Genotype Homeostasis Intestinal Mucosa Male Mice Mice, Knockout Niacin Peptidyl-Dipeptidase A Time Factors Defective intestinal amino acid absorption in Ace2 null mice. http://purl.org/coar/resource_type/c_6501