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Sulfate ions in mammalian physiology: lessons from sulfate transporter null mice
Author(s) -
Dawson Paul Anthony,
McGuckin Michael A,
Markovich Daniel
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a531-b
Subject(s) - mucin , colitis , sulfate , microbiology and biotechnology , biology , transporter , immunology , physiology , chemistry , biochemistry , gene , organic chemistry
The NaS1 sulfate transporter maintains serum sulfate levels. Several polymorphisms (SNPs) exist in human NaS1, including R12X and N174S. NaS1 null (Nas1−/−) mice exhibit hyposulfatemia and a decreased sulfate content of intestinal mucins. This is relevant to gastrointestinal (GI) physiology because sulfate plays a role in protecting mucins from degradation. Our aims were to functionally characterise human NaS1 SNPs and to determine the effects of hyposulfatemia in Nas1−/− mice on GI physiology. Compared to wild‐type NaS1, R12X and N174S led to 100% & 60% loss of function, respectively. Nas1−/− and Nas1+/+ mice were challenged orally with C. jejuni bacteria or dextran sodium sulfate (DSS), a model for inducing colitis. C. jejuni colonised stomach and intestines of Nas1−/− (n=16) and Nas1+/+ (n=16) mice. One Nas1+/+ and 9 Nas1−/− mice developed systemic infection. DSS treatment (2.5% 7 days) led to shorter intestines (by 15% P <0.01) and decreased hematocrit (by 25% P <0.05) in Nas1−/− mice, suggesting hyposulfatemia enhances DSS‐induced colitis and intestinal bleeding. In summary, we characterized 2 loss of function SNPs in human NaS1 and showed that Nas1−/− mice have reduced defence from mucosal bacterial infection, and are more susceptible to DSS‐induced colitis. These findings underline the importance of sulfated mucins in intestinal barrier function, and prompt studies of GI mucins in humans with NaS1 SNPs.