{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:33:52Z","timestamp":1791718432476,"version":"4.3.4"},"reference-count":37,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2012,9,15]]},"abstract":"<jats:p>Mutations in the main intestinal and kidney luminal neutral amino acid transporter B<jats:sup>0<\/jats:sup>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<jats:sup>0<\/jats:sup>AT1 expression, we tested the impact of intestinal B<jats:sup>0<\/jats:sup>AT1 absence in ace2 null mice. Their weight gain following weaning was decreased, and Na<jats:sup>+<\/jats:sup>-dependent uptake of B<jats:sup>0<\/jats:sup>AT1 substrates measured in everted intestinal rings was defective. Additionally, high-affinity Na<jats:sup>+<\/jats:sup>-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<jats:sup>0<\/jats:sup>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.<\/jats:p>","DOI":"10.1152\/ajpgi.00140.2012","type":"journal-article","created":{"date-parts":[[2012,7,13]],"date-time":"2012-07-13T19:06:31Z","timestamp":1342206391000},"page":"G686-G695","source":"Crossref","is-referenced-by-count":110,"title":["Defective intestinal amino acid absorption in Ace2 null mice"],"prefix":"10.1152","volume":"303","author":[{"given":"Dustin","family":"Singer","sequence":"first","affiliation":[{"name":"Institute of Physiology and Z\u00fcrich Center for Integrative Human Physiology, University of Z\u00fcrich, Zurich, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone M. 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